ArticleLiterature Review

The antioxidant role of coenzyme Q. Mitochondrion 7:S41-S50

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

A number of functions for coenzyme Q (CoQ) have been established during the years but its role as an effective antioxidant of the cellular membranes remains of dominating interest. This compound is our only endogenously synthesized lipid soluble antioxidant, present in all membranes and exceeding both in amount and efficiency that of other antioxidants. The protective effect is extended to lipids, proteins and DNA mainly because of its close localization to the oxidative events and the effective regeneration by continuous reduction at all locations. Its biosynthesis is influenced by nuclear receptors which may give the possibility, in the future, by using agonists or antagonists, of reestablishing the normal level in deficiencies caused by genetic mutations, aging or cardiomyopathy. An increase in CoQ concentration in specific cellular compartments in the presence of various types of oxidative stress appears to be of considerable interest.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Coenzyme Q10 (CoQ10), also known as ubiquinone or a super-vitamin (vitamin Q), is a potential candidate found normally in the biological system in most cells, where it is involved in the electron transport chain (ETC), ATP generation, and regenerated vitamin E, and it also has ability as an antioxidant [21][22][23][24][25]. Because CoQ10 is produced in inadequate quantities in the body, particularly during times of stress, it must be acquired from an external source [26]. ...
... Eco-friendly natural techniques have drawn researchers' interest as viable and effective alternatives to antibiotics [33][34][35][36]. Coenzyme Q10 (CoQ10) or ubiquinone is one probable model present naturally in the biological system and most cells with antioxidant potentials [24,25,[37][38][39]. ...
... In this context, CoQ10 s function in the Krebs cycle makes it a critical piece of carbohydrate, protein, and lipid metabolism [21][22][23]. Furthermore, the indirect impact of CoQ10 on hormones function (insulin, glucagon, and cortisone) and/or vitamin E re-generation assists in altering the metabolic rate [24,25,37,38,41]. Changes in the histological composition of the gut support the overgrowth in the C5. ...
Article
Full-text available
Red tilapia eggs one day post fertilization (dpf) were exposed to coenzyme Q10 (CoQ10) at rates of 0, 5, and 10 mg/L for control, treatment 2 (C5), and treatment 3 (C10), respectively, without exchanging water and until the larval mouth-opening stage. Fertilized eggs of red tilapia exposed to different concentrations of CoQ10 were hatched at rates (p > 0.05) between 38 to 54.67%. The yolk-sac diameter at the 2nd day post hatching (dph), ranged from 1.85 to 1.87 mm in depth and 1.63 to 1.88 mm in width and was not altered by the CoQ10 treatments. Similarly, red tilapia survival (p > 0.05) ranged from 22.67 to 32%. On 6 dph, a slight percentage (2.08%) of survived fishes exposed to high CoQ10 dose (C10) exhibited larval deformation in the form of an axial curvature of the spine in the abdominal and caudal region. Larvae displayed a normal structure of the esophagus folds in all fish groups, and larvae in the C5 group displayed the longest folds and widest muscularis layer, followed by fishes in the C10 group and the control. Red tilapia fry on 30 dph treated with CoQ10 possessed higher antioxidant potentials in terms of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) compared to the control. In conclusion, treating Red tilapia fertile eggs with 5 mg/L CoQ10 improves the growth, gut structure, and antioxidant efficiency of the produced larvae.
... Coenzyme Q10 (CoQ10, ubiquinone) is a lipid soluble compound present in the majority of living cells. In humans, once administered per os it is absorbed in the gut and reduced in the liver to its active form, Q10-ubiquinol, which acts as a diffusible electron carrier in the mitochondrial respiratory chain, and as an antioxidant removing free radicals (22)(23)(24). CoQ10 has been proven effective in diverse experimental disease paradigms of oxidative stress (25)(26)(27). Therefore, by increasing energy production and antioxidant capacity, CoQ10 is predicted to limit the damage generated by the neuroinflammationm microglial activation, and excitotoxicity well documented in ASD brains, ultimately leading to excessive neuritic pruning and/or cell apoptosis (28,29). ...
... Coenzyme Q10 is a lipid soluble compound synthesized by our organism and also introduced in small amounts through the diet. It acts as an electron acceptor donor, by oscillating between its oxidized (ubiquinone) and reduced (ubiquinol) forms (22)(23)(24). This redox activity sustains mitochondrial homeostasis and prevents free radical generation. ...
... This redox activity sustains mitochondrial homeostasis and prevents free radical generation. Therefore, CoQ 10 is recognized as an intracellular antioxidant that protects membrane phospholipids, mitochondrial membrane proteins, and low-density lipoproteins from the oxidative damage produced by free radicals (22)(23)(24). Furthermore, intra-mitochondrial concentrations of CoQ 10 largely influence the efficiency of the mitochondrial respiratory chain. ...
Article
Full-text available
Increased oxidative stress and defective mitochondrial functioning are shared features among many brain disorders. The aim of this study was to verify retrospectively the clinical efficacy and safety of a metabolic support therapy with Q10 ubiquinol, vitamin E and complex-B vitamins in various neurodevelopmental disorders. This retrospective chart review study included 59 patients (mean age 10.1 ± 1.2 y.o., range 2.5–39 years; M:F = 2.47:1), diagnosed with Autism Spectrum Disorder ( n = 17), Autism Spectrum Disorder with co-morbid Intellectual Disability ( n = 19), Intellectual Disability or Global Developmental Delay ( n = 15), Attention-Deficit/Hyperactivity Disorder ( n = 3) and Intellectual Disability in Phelan-McDermid syndrome due to chr. 22q13.33 deletion ( n = 5). After a minimum of 3 months of therapy, a positive outcome was recorded in 45/59 (76.27%) patients, with Clinical Global Impression—Improvement scores ranging between 1 (“very much improved”) and 3 (“minimally improved”). The most widespread improvements were recorded in cognition ( n = 26, 44.1%), adaptative functioning ( n = 26, 44.1%) and social motivation ( n = 19, 32.2%). Improvement rates differed by diagnosis, being observed most consistently in Phelan-McDermid Syndrome (5/5, 100%), followed by Intellectual Disability/Global Developmental Delay (13/15, 86.7%), Autism Spectrum Disorder with co-morbid Intellectual Disability (15/19, 78.9%), Autism Spectrum Disorder (11/17, 64.7%) and ADHD (1/3, 33.3%). No significant adverse event or side effect leading to treatment discontinuation were recorded. Mild side effects were reported in 18 (30.5%) patients, with the most frequent being increased hyperactivity (9/59, 15.3%). This retrospective chart review suggests that metabolic support therapy with Q10 ubiquinol, vitamin E and complex-B vitamins is well tolerated and produces some improvement in the majority of patients with neurodevelopmental disorders, especially in the presence of intellectual disability. Randomized controlled trials for each single neurodevelopmental disorder are now warranted to conclusively demonstrate the efficacy of these mitochondrial bioenergetic and antioxidant agents and to estimate their therapeutic effect size.
... Coenzyme Q10 (CoQ10) is an electron carrier in the mitochondrial ETC, transferring electrons from complex I and II to complex III during oxidative phosphorylation (OX-PHOS). It also prevents cellular damage by exerting potent antioxidative activity [15]. Depletion of endogenous CoQ10 content in mitochondria of the skeletal muscle occurs in aging [16]. ...
... Clinically, postoperative morphine consumption at 24 and 48 h was significantly lower in the CoQ10 group when compared to the control and CoQ10 + IPC groups (Median [P25-P75] at 24 h; CoQ10 3.5 [1][2][3][4][5][6] vs. placebo 6 [5][6][7][8][9][10][11][12][13][14][15] vs. CoQ10 + IPC 9 [6-13.5] mg, p = 0.037) ( Figure 5A). ...
... This finding indicated that CoQ10 potentially prevents the protective effect of the IPC. It is possibly because CoQ10 is effective in preventing lipid peroxidation [15] and inhibiting the MAPK/ERK signaling pathway [52]. ...
Article
Full-text available
Tourniquet (TQ) use during total knee arthroplasty (TKA) induces ischemia/reperfusion (I/R) injury, resulting in mitochondrial dysfunction. This study aims to determine the effects of coenzyme Q10 (CoQ10) and ischemic preconditioning (IPC), either alone or in combination, on I/R-induced mitochondrial respiration alteration in peripheral blood mononuclear cells (PBMCs) and pain following TKA. Forty-four patients were allocated into four groups: control, CoQ10, IPC, and CoQ10 + IPC. CoQ10 dose was 300 mg/day for 28 days. IPC protocol was three cycles of 5/5-min I/R time. Mitochondrial oxygen consumption rates (OCRs) of PBMCs were measured seven times, at baseline and during ischemic/reperfusion phases, with XFe 96 extracellular flux analyzer. Postoperative pain was assessed for 48 h. CoQ10 improved baseline mitochondrial uncoupling state; however, changes in OCRs during the early phase of I/R were not significantly different from the placebo. Compared to ischemic data, IPC transiently increased basal OCR and ATP production at 2 h after reperfusion. Clinically, CoQ10 significantly decreased pain scores and morphine requirements at 24 h. CoQ10 + IPC abolished analgesic effect of CoQ10 and mitochondrial protection of IPC. In TKA with TQ, IPC enhanced mitochondrial function by a transient increase in basal and ATP-linked respiration, and CoQ10 provides postoperative analgesic effect. Surprisingly, CoQ10 + IPC interferes with beneficial effects of each intervention.
... Isoprene units of the chain are species-specific: human isoform mainly encloses ten isoprene units (CoQ 10 ). In rodents, this molecule presents mainly nine units (CoQ 9 ), and around a 10% has ten units (CoQ 10 ). The yeast Saccharomyces cerevisiae holds six units (CoQ 6 ), whereas Schizosaccharomyces pombe contains ten units (CoQ 10 ). ...
... In rodents, this molecule presents mainly nine units (CoQ 9 ), and around a 10% has ten units (CoQ 10 ). The yeast Saccharomyces cerevisiae holds six units (CoQ 6 ), whereas Schizosaccharomyces pombe contains ten units (CoQ 10 ). Bacteria such as Escherichia coli contains eight isoprene units (CoQ 8 ) [5]. ...
Article
Full-text available
Coenzyme Q is a unique lipidic molecule highly conserved in evolution and essential to maintaining aerobic metabolism. It is endogenously synthesized in all cells by a very complex pathway involving a group of nuclear genes that share high homology among species. This pathway is tightly regulated at transcription and translation, but also by environment and energy requirements. Here, we review how coenzyme Q reacts within mitochondria to promote ATP synthesis and also integrates a plethora of metabolic pathways and regulates mitochondrial oxidative stress. Coenzyme Q is also located in all cellular membranes and plasma lipoproteins in which it exerts antioxidant function, and its reaction with different extramitochondrial oxidoreductases contributes to regulate the cellular redox homeostasis and cytosolic oxidative stress, providing a key factor in controlling various apoptosis mechanisms. Coenzyme Q levels can be decreased in humans by defects in the biosynthesis pathway or by mitochondrial or cytosolic dysfunctions, leading to a highly heterogeneous group of mitochondrial diseases included in the coenzyme Q deficiency syndrome. We also review the importance of coenzyme Q levels and its reactions involved in aging and age-associated metabolic disorders, and how the strategy of its supplementation has had benefits for combating these diseases and for physical performance in aging.
... Then, after several years of research, it was discovered that Plasma Membrane Oxidase is a complex system, now indicated as Plasma Membrane Redox System (PMRS), involving different components; it serves as terminal oxidase for the cytosolic NADH and is responsible for the protein disulfide-thiol interchange activity on the outside of the plasmamembrane. Moreover, CoQ is a modulator of the mitochondrial transition permeability pore (mPTP) [14], is involved in gene regulation [15], and displays anti-inflammatory effects by influencing the expression of NFκ-β1-dependent genes [16][17][18][19]. In the reduced form, CoQ is a powerful antioxidant whose efficiency depends on its intramembranous distribution and the presence of many intracellular CoQ reducing enzymes. ...
... The exceptionally high antioxidant efficiency of CoQ is due to its intra-membrane localization, its general and abundant distribution, and its effective reduction/reactivation by several cellular systems that catalyze its reduction to the active form [16]. In mitochondria, the antioxidant reduced form of CoQ is regenerated directly by the respiratory chain [19]. In addition to the mitochondrial respiratory chain, the PMRS also exerts the same function, generating ubiquinol by transferring two electrons in a two single-step mechanism (CytB5R3) [61] or by direct two-electrons quinone reduction (NQO1) [62]; this last mechanism avoids the formation of a semiquinone intermediate (Figure 3). ...
Article
Full-text available
Coenzyme Q (CoQ) is a key component of the respiratory chain of all eukaryotic cells. Its function is closely related to mitochondrial respiration, where it acts as an electron transporter. However, the cellular functions of coenzyme Q are multiple: it is present in all cell membranes, limiting the toxic effect of free radicals, it is a component of LDL, it is involved in the aging process, and its deficiency is linked to several diseases. Recently, it has been proposed that coenzyme Q contributes to suppressing ferroptosis, a type of iron-dependent programmed cell death characterized by lipid peroxidation. In this review, we report the latest hypotheses and theories analyzing the multiple functions of coenzyme Q. The complete knowledge of the various cellular CoQ functions is essential to provide a rational basis for its possible therapeutic use, not only in diseases characterized by primary CoQ deficiency, but also in large number of diseases in which its secondary deficiency has been found.
... Coenzyme Q10 (CQ10) is a potent free radical scavenger and antioxidant found naturally in the mitochondrial inner membrane of most cells in the biological system (Nepal et al., 2010). In favor of CQ10's strong antioxidant amplitude, it could efficiently protect the cells membrane, DNA, proteins, and lipids from oxidative damage, aids vitamin E regeneration, and support fit levels of energy (Bentinger et al., 2007;Linnane et al., 2007;Martin et al., 2007). CQ10 displayed favorable pharmacological activities in several diseases, including muscular dystrophy, cancer, diabetes, obesity, and heart disease (Kumar et al., 2007b;Roffe et al., 2004;Sohet et al., 2009). ...
... Interaction effect (water pollution x feed additive) Control Non supplemented 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 c ± 0.00 0.00 c ± 0.00 0.00 c ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 b ± 0.00 0.00 ± 0.00 0.00 c ± 0.00 0.00 c ± 0.00 0.00 ± 0.00 0.00 ± 0.00 SM 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 c ± 0.00 0.00 c ± 0.00 0.00 c ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 b ± 0.00 0.00 ± 0.00 0.00 c ± 0.00 0.00 c ± 0.00 0.00 ± 0.00 0.00 ± 0.00 CQ10 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 c ± 0.00 0.00 c ± 0.00 0.00 c ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 b ± 0.00 0.00 ± 0.00 0.00 c ± 0.00 0.00 c ± 0.00 0.00 ± 0.00 0.00 ± 0.00 SM + CQ10 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 c ± 0.00 0.00 c ± 0.00 0.00 c ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 b ± 0.00 0.00 ± 0.00 0.00 c ± 0.00 0.00 c ± 0.00 0.00 ± 0.00 0.00 ± 0.00 Fluoride Non supplemented 0.60 ± 0.22 1.20 ± 0.49 1.00 ± 0.47 0.20 ± 0.20 3.30 a ± 0.54 1.50 a ± 0.17 3.00 a ± 0.45 0.20 ± 0.13 0.70 ± 0.21 2.20 a ± 0.33 0.30 ± 0.21 0.70 a ± 0.26 2.00 a ± 0.42 0.20 ± 0.20 0.40 ± 0.27 SM 0.20 ± 0.13 0.30 ± 0.30 0.30 ± 0.15 0.00 ± 0.00 1.40 b ± 0.37 1.00 b ± 0.21 0.60 c ± 0.40 0.20 ± 0.13 0.30 ± 0.15 0.60 b ± 0.27 0.00 ± 0.00 0.20 bc ± 0.13 0.80 b ± 0.33 0.00 ± 0.00 0.00 ± 0.00 CQ10 0.30 ± 0.15 0.90 ± 0.46 0.80 ± 0.36 0.00 ± 0.00 3.00 a ± 0.47 1.00 b ± 0.21 2.10 b ± 0.46 0.10 ± 0.10 0.60 ± 0.22 1.80 a ± 0.25 0.20 ± 0.13 0.40 ab ± 0.16 1.60 a ± 0.40 0.20 ± 0.20 0.20 ± 0.20 SM + CQ10 0.10 ± 0.10 0.00 ± 0.00 0.20 ± 0.13 0.00 ± 0.00 1.00 bc ± 0.42 0.60 b ± 0.22 0.30 c ± 0.30 0.00 ± 0.00 0.10 ± 0.10 0.40 b ± 0.22 0.00 ± 0.00 0.00 c ± 0.00 0.20 bc ± 0.20 0.00 ± 0.00 0.00 ± 0.00 improved growth and feed utilization. This could be because of modifying the microflora diversity or CQ10 anti-inflammatory activity (Schmelzer et al., 2008) or due to the indirect effect of CQ10 on resynthesis of vitamin E (Bentinger et al., 2007;Linnane et al., 2007). Besides, the CQ10 role in the electron transport chain could efficiently affect the metabolism of protein, carbohydrates, and lipids (Lenaz et al., 2007;Shukla and Dubey, 2018). ...
Article
High fluoride (FL) concentration in many areas of the world is of great concern. It poses a threat to aquatic life. Therefore, the current study was operated to scrutinize the efficiency of Silybum marianum (SM) and/or coenzyme Q10 (CQ10) dietary supplementation to rescue FL negative effects on the growth, hematological indicators, liver and kidney function, serum protein profile, innate immune parameters, oxidative status, vital organ architecture, and disease resistance to Aeromonas sobria. Two hundred and forty healthy Clarias gariepinus fish were alienated into eight groups in triplicate. The control group was fed a non-supplemented basal diet. The SM, CQ10, and SM + CQ10 groups were fed a basal diet fortified with 10 g SM/kg diet, 40 mg CQ10/kg diet, or SM + CQ10, respectively. The FL group was exposed to 73.45 mg FL /L water. The FL + SM, FL + CQ10, and FL + SM + CQ10 were exposed to FL concomitantly with SM, CQ10, and SM + CQ10, respectively. The experiment continued for 60 successive days. The results showed lower weight gain and specific growth rate but higher hepatosomtic index in the FL-exposed fish. An obvious leukopenic and anemic condition was detected. Also, a significant increase in the serum levels of hepatic enzymes and kidney damage products was apparent in FL-exposed fish. Nevertheless, exhaustion of the non-enzymatic and enzymatic antioxidants but elevated lipid peroxidation product (MDA) was noted. The FL exposure exhausted lysozyme activity, complement 3, nitric oxide, total proteins, albumin, and γ globulin contents in the serum of C. gariepinus. Moreover, diverse pathological alterations were detected in the liver, kidney, and spleen. After 14 days of A. sobria challenge, the relative survival rate percentage was significantly reduced in FL-exposed fish. On the contrary, the SM and/or CQ10 addition significantly reduced most FL-associated negative impacts. Conclusively, SM and/or CQ10 dietary supplements could be beneficial for alleviating FL deleterious impacts, thus affording advantageous aqua feed additive for C. gariepinus.
... Coenzyme Q 10 (CoQ10) CoQ10, also known as ubiquinone, is a key antioxidant for cell function that decreases ROS production. It is a fat-soluble micronutrient synthesized by all human cells and tissues that can also be taken exogenously to mitigate ROS damage, as CoQ10 is able to reduce superoxide production in mitochondria 176,177 . CoQ10 has an important role in the mitochondrial electron transport chain, as it accepts and transfers electrons between complexes I-III 178 . ...
... Additionally, CoQ10 participates in a variety of functions inside the cell. CoQ10 is able to prevent damage to DNA and proteins, lipid peroxidation, stabilize calcium channels to stop their overload, activate the uncoupling proteins for heat generation, increase cyclic adenosine monophosphate (cAMP) levels, and enhance the activity of SIRT1 and PGC-1α, which have important roles in improving mitochondrial biogenesis and function 176,[179][180][181] . Numerous studies have shown that the intake of exogenous CoQ10 could help to prevent the progression of illness, such as heart failure, metabolic syndrome, NAFLD, diabetes mellitus, and several neurodegenerative diseases 177,[181][182][183][184][185][186] . ...
Article
Full-text available
Exposure to microgravity and ionizing radiation during spaceflight missions causes excessive reactive oxygen species (ROS) production that contributes to cellular stress and damage in astronauts. Average spaceflight mission time is expected to lengthen as humanity aims to visit other planets. However, longer missions or spaceflights will undoubtedly lead to an increment in microgravity, ionizing radiation and ROS production. Strategies to minimize ROS damage are necessary to maintain the health of astronauts, future space colonists, and tourists during and after spaceflight missions. An antioxidant cocktail formulated to prevent or mitigate ROS damage during space exploration could help maintain the health of space explorers. We propose key points to consider when developing an antioxidant cocktail. We discuss how ROS damages our body and organs, the genetic predisposition of astronauts to its damage, characteristics and evidence of the effectiveness of antioxidants to combat excess ROS, differences in drug metabolism when on Earth and in space that could modify antioxidant effects, and the characteristics and efficacy of common antioxidants. Based on this information we propose a workflow for assessing astronaut resistance to ROS damage, infight monitoring of ROS production, and an antioxidant cocktail. Developing an antioxidant cocktail represents a big challenge to translate current medical practices from an Earth setting to space. The key points presented in this review could promote the development of different antioxidant formulations to maintain space explorers’ health in the future.
... The scale consists of 14 items featuring groups of psychological and somatic symptoms related to experienced agitation and stress. Each group of items is evaluated on a scale from 0 to 4. The total score indicates mild (≤ 17), mild to moderate (18)(19)(20)(21)(22)(23)(24), or moderate to severe (25)(26)(27)(28)(29)(30) anxiety [17]. ...
... Studies into the effects of CoQ10 supplementation have reported significant antiinflammatory benefits when used as adjuvant therapy prior to heart surgery [25,26]. Also, the monocyte-T-lymphocyte, cytokine or inflammatory hypothesis of depression was confirmed as researchers were able to demonstrate the relationship between inflammatory and oxidative stress, on one hand and depressive mental states on the other [27]. ...
Article
Full-text available
(1) Background: The heart-type fatty acid-binding protein (H-FABP) is a specific myocardial biomarker and high levels indicate ischemia regardless of patient-reported symptoms. Concurrently, major adverse cardiovascular events and surgery such as coronary artery by-pass grafting (CABG) cause substantial psycho-emotional distress e.g., depression and anxiety. Comprehensive cardiac rehabilitation is, therefore, essential to both physical and psychological recovery. (2) Methods: This is a unicentric, prospective study on 120 consecutive post-CABG patients undergoing a 6-month cardiac rehabilitation program based on physical exercise, Mediterranean diet principles, and Q10 coenzyme antioxidant supplements. H-FABP levels, depression, and anxiety scores (Hamilton HAM-D and HAM-A scales) were monitored after surgery and at 6 months. (3) Results: Mean H-FABP dropped from 60.56 to 4.81. Physical ability increased from 1–2 to 4–5 METS. Mean depression and anxiety improved from 15.88 to 6.96 and from 25.13 to 15.68, respectively. Median scores went down 50% for depression and 9% for anxiety. Explored associations between H-FABP and psycho-emotional status were statistically insignificant. (4) Conclusions: patients adhered to the program and improved significantly in all studied aspects. Clinical significance is discussed in the context of countries like Romania, where such programs are limited by systemic and financial constraints. Further research directions are identified.
... Coenzyme Q Coenzyme Q 10 (CoQ 10 ) is a lipid-soluble antioxidant essential to mitochondrial electron transport chain (ETC) function and facilitates the transport of electrons from complex I and II to complex III [30]. As an antioxidant, CoQ 10 directly reduces the initiation and propagation of lipid peroxidation by preventing lipid peroxyl radical production, as well as indirectly by regenerating other antioxidants such α-tocopherol (Vitamin E) and ascorbate (Vitamin C) [31,32]. CoQ 10 is present in all intracellular membranes; however, as a component of the oxidative phosphorylation pathway, it is especially well placed in mitochondria, where electron leakage contributes to cellular superoxide and hydrogen peroxide production, to inhibit protein and DNA oxidation by both a general ROS scavenging mechanism as well as functioning as a chain-breaking antioxidant to prevent free radical propagation [32]. ...
... As an antioxidant, CoQ 10 directly reduces the initiation and propagation of lipid peroxidation by preventing lipid peroxyl radical production, as well as indirectly by regenerating other antioxidants such α-tocopherol (Vitamin E) and ascorbate (Vitamin C) [31,32]. CoQ 10 is present in all intracellular membranes; however, as a component of the oxidative phosphorylation pathway, it is especially well placed in mitochondria, where electron leakage contributes to cellular superoxide and hydrogen peroxide production, to inhibit protein and DNA oxidation by both a general ROS scavenging mechanism as well as functioning as a chain-breaking antioxidant to prevent free radical propagation [32]. ...
Article
Full-text available
Parkinson's disease (PD) is a progressive neurodegenerative disorder that arises due to a complex and variable interplay between elements including age, genetic, and environmental risk factors that manifest as the loss of dopaminergic neurons. Contemporary treatments for PD do not prevent or reverse the extent of neurodegeneration that is characteristic of this disorder and accordingly, there is a strong need to develop new approaches which address the underlying disease process and provide benefit to patients with this debilitating disorder. Mitochondrial dysfunction, oxidative damage, and inflammation have been implicated as pathophysiological mechanisms underlying the selective loss of dopaminergic neurons seen in PD. However, results of studies aiming to inhibit these pathways have shown variable success, and outcomes from large-scale clinical trials are not available or report varying success for the interventions studied. Overall, the available data suggest that further development and testing of novel therapies are required to identify new potential therapies for combating PD. Herein, this review reports on the most recent development of antioxidant and anti-inflammatory approaches that have shown positive benefit in cell and animal models of disease with a focus on supplementation with natural product therapies and selected synthetic drugs.
... Moreover, it has also been shown that CoQ 10 is involved in uncoupling of proteins as well as in modulating the mitochondrial permeability transition pore (MPTP). Furthermore, in its reduced form, ubiquinol is endowed with antioxidant properties by acting as a chain-breaker of peroxidative processes that occur in biological membranes [25]. Ubiquinol is also a crucial component of the plasma membrane reducing system (PMRS) enabling the recycling of lipophilic vitamin E and sparing hydrophilic vitamin C [26,27]. ...
... The antioxidant property of any compound is represented when it prevents oxidative stress-induced cell death [27]. Various analogs of CoQ 0 have shown antioxidant or proantioxidant properties [28,29]. CoQ 0 is a coenzyme and redoxactive compound without an isoprenoid side chain occurring mostly within mitochondria that suppresses the activity of complex 1 of the mitochondrial respiratory chain and prevents the opening of the mitochondrial permeability transition pore [30]. ...
Article
Full-text available
Coenzyme Q (CoQ) analogs with a variable number of isoprenoid units have exhibited as anti-inflammatory as well as antioxidant molecules. Using novel quinone derivative CoQ0 (2,3-dimethoxy-5-methyl-1,4-benzoquinone, zero side chain isoprenoid), we studied its molecular activities against LPS/ATP-induced inflammation and redox imbalance in murine RAW264.7 macrophages. CoQ0’s non- or subcytotoxic concentration suppressed the NLRP3 inflammasome and procaspase-1 activation, followed by downregulation of IL1β expression in LPS/ATP-stimulated RAW264.7 macrophages. Similarly, treatment of CoQ0 led to LC3-I/II accumulation and p62/SQSTM1 activation. An increase in the Beclin-1/Bcl-2 ratio and a decrease in the expression of phosphorylated PI3K/AKT, p70 S6 kinase, and mTOR showed that autophagy was activated. Besides, CoQ0 increased Parkin protein to recruit damaged mitochondria and induced mitophagy in LPS/ATP-stimulated RAW264.7 macrophages. CoQ0 inhibited LPS/ATP-stimulated ROS generation in RAW264.7 macrophages. Notably, when LPS/ATP-stimulated RAW264.7 macrophages were treated with CoQ0, Mito-TEMPO (a mitochondrial ROS inhibitor), or N-acetylcysteine (NAC, a ROS inhibitor), there was a significant reduction of LPS/ATP-stimulated NLRP3 inflammasome activation and IL1β expression. Interestingly, treatment with CoQ0 or Mito-TEMPO, but not NAC, significantly increased LPS/ATP-induced LC3-II accumulation indicating that mitophagy plays a key role in the regulation of CoQ0-inhibited NLRP3 inflammasome activation. Nrf2 knockdown significantly decreased IL1β expression in LPS/ATP-stimulated RAW264.7 macrophages suggesting that CoQ0 inhibited ROS-mediated NLRP3 inflammasome activation and IL1β expression was suppressed due to the Nrf2 activation. Hence, this study showed that CoQ0 might be a promising candidate for the therapeutics of inflammatory disorders due to its effective anti-inflammatory as well as antioxidant properties.
... Though reasonably stable, lipid peroxides may be decomposed by metal complexes in a reaction catalysed by transition metals producing radicals that can reinitiate peroxidation via redox cycling of the metal ions, forming products, such as 4-hydroxy-2-nonenal (4HNE), 4-hydroxyhexenal (4-HHE), and malonaldehyde (MDA), which are useful and extensively studied biomarkers of lipid peroxidation [75,82,83,89]. These aldehydes, in turn, bind with DNA or protein, causing more severe damage [90]. Loss of membrane integrity, breakdown of organelles, oxidation and impairment of DNA, RNA, and proteins result where there is severe lipid peroxidation reaction [76,88]. ...
Article
Full-text available
The maintenance of seed quality during the long-term conservation of plant genetic resources is crucial for averting the projected food crises that are linked to the changing climate and rising world population. However, ageing-induced loss of seed vigour and viability during storage remains an inevitable process that compromises productivity in several orthodox-seeded crop species. Seed ageing under prolonged storage, which can occur even under optimal conditions, induces several modifications capable of causing loss of intrinsic physiological quality traits, including germination capacity and vigour, and stand establishment. The problems posed by seed ageing have motivated the development of various techniques for mitigating their detrimental effects. These invigoration techniques generally fall within one of two categories: (1) priming or pre-hydrating seeds in a solution for improved post-harvest performance, or (2) post-storage reinvigoration which often involves soaking seeds recovered from storage in a solution. Seed priming methods are generally divided into classical (hydropriming, osmopriming, redox priming, biostimulant priming, etc.) and advanced (nanopriming, magnetopriming and priming using other physical agents) techniques. With the increasing popularity of seed invigoration techniques to achieve the much-desired enhanced productivity and resilience in the face of a changing climate, there is an urgent need to explore these techniques effectively (in addition to other important practices such as plant breeding, fertilizer application, and the control of pests and diseases). This review aims to provide an overview of ageing in orthodox seeds and invigoration techniques that can enhance desirable agronomic and physiological characters.
... Q is a central component of the mtETS (Crane et al 1959;Hatefi et al 1959, Mitchell 1961 and is involved in antioxidant defense (Noh et al 2013), mitophagy (Rodríguez-Hernández et al 2009), and regulation of permeability transition (Balaban et al 2005;Bentinger et al 2007;Fontaine et al 1998;Lopez-Lluch et al 2010). Several branches of the ETS converge at the Q-junction: In mammalian mitochondria, ETS-reactive Q (redox active, Qra; Kröger, Klingenberg 1973a) is reduced by electron supply from (1) Complex I (CI), (2) CII, (3) electron-transferring flavoprotein Complex, (4) mt-glycerophosphate dehydrogenase Complex, (5) dihydro-orotate dehydrogenase Complex, and from other enzyme complexes (Enriquez, Lenaz 2014;Gnaiger 2020). ...
Article
Full-text available
Redox states of the mitochondrial coenzyme Q pool, which reacts with the electron transfer system, reflect the balance between (1) reducing capacities of electron flow from fuel substrates converging at the Q-junction, (2) oxidative capacities downstream of Q to O2, and (3) the load on the OXPHOS system utilizing or dissipating the protonmotive force. A three-electrode sensor (Rich 1988; Moore et al 1988) was implemented into the NextGen-O2k to monitor continuously the redox state of CoQ2 added as a Q-mimetic simultaneously with O2 consumption. The Q-Module was optimized for high signal-to-noise ratio, minimum drift, and minimum oxygen diffusion. CoQ2 equilibrates in the same manner as Q at Complexes CI, CII and CIII. The CoQ2 redox state is monitored amperometrically with the working electrode, which is poised at CoQ2 redox peak potentials determined by cyclic voltammetry. The voltammogram also provides quality control of the Q-sensor and reveals chemical interferences. The CoQ2 redox state and O2 consumption were measured simultaneously in isolated mouse cardiac and brain mitochondria. CoQ2 ― and by implication mitochondrial Q ― was more oxidized when O2 flux was stimulated by coupling control: when energy demand increased from LEAK to OXPHOS and electron transfer capacities in the succinate pathway. In contrast, CoQ2 was more reduced when O2 flux was stimulated by pathway-control of electron input capacities, increasing from the NADH (N)- to succinate (S)-linked pathway which converge at the Q-junction, with CI-Q-CIII and CII-Q-CIII segments, respectively. N- and S- respiratory pathway capacities were not completely additive, compatible with partitioning of Q intermediary between the solid-state and liquid-state models of supercomplex organization. The direct proportionality of CoQ2 reduction and electron input capacities through the CI-Q-CIII and CII-Q-CIII segments suggests that CoQ2 is accurately mimicking mitochondrial Q-redox changes.
... Coenzyme Q (CoQ) has been studied in detail, especially as a member of the respiratory chain in mitochondria [1]. Another main function of CoQ is participation in many cellular processes, such as antioxidant processes [1,2]. Consequently, CoQ plays important roles in maintaining cellular life and normal functions of the living organism [3]. ...
Article
Full-text available
Hyperglycemia, hyperlipidemia, and adiposity are the main factors that cause inflammation in type 2 diabetes due to excessive ROS production, leading to late complications. To counteract the effects of increased free radical production, we searched for a compound with effective antioxidant properties that can induce coenzyme Q biosynthesis without affecting normal cellular functions. Tocotrienols are members of the vitamin E family, well-known as efficient antioxidants that are more effective than tocopherols. Deh-T3β is a modified form of the naturally occurring tocotrienol-β. The synthesis of this compound involves the sequential modification of geranylgeraniol. In this study, we investigated the effects of this compound in different experimental models of diabetes complications. Deh-T3β was found to possess multifaceted capacities. In addition to enhanced wound healing, deh-T3β improved kidney and liver functions, reduced liver steatosis, and improved heart recovery after ischemia and insulin sensitivity in adipose tissue in a mice model of type 2 diabetes. Deh-T3β exerts these positive effects in several organs of the diabetic mice without reducing the non-fasting blood glucose levels, suggesting that both its antioxidant properties and improvement in mitochondrial function are involved, which are central to reducing diabetes complications.
... Recent evidence points to a key role of ferroptosis suppressor protein 1 (FSP1) in inhibiting ferroptosis, by directly reducing the oxidized endogenous molecule coenzyme Q10 (CoQ10) with NADH as a cofactor [148]. Cancer cell lines stably expressing FSP1 were reported to be preserved from ferroptosis, including from that caused by GPX4 inhibitors [148] and reduced CoQ10 was assessed to work as a lipophilic RTA in the plasma membrane [149]. In this context, it was shown that idebenone, a hydrophilic reduced analog of CoQ10, could inhibit FIN56-induced ferroptosis, while the supplementation of CoQ10 was found to be ineffective owing to its high hydrophobicity [150]. ...
Article
Full-text available
Even though COVID-19 is mostly well-known for affecting respiratory pathology, it can also result in several extrapulmonary manifestations, leading to multiorgan damage. A recent reported case of SARS-CoV-2 myocarditis with cardiogenic shock showed a signature of myocardial and kidney ferroptosis, a novel, iron-dependent programmed cell death. The term ferroptosis was coined in the last decade to describe the form of cell death induced by the small molecule erastin. As a specific inducer of ferroptosis, erastin inhibits cystine-glutamate antiporter system Xc-, blocking transportation into the cytoplasm of cystine, a precursor of glutathione (GSH) in exchange with glutamate and the consequent malfunction of GPX4. Ferroptosis is also promoted by intracellular iron overload and by the iron-dependent accumulation of polyunsaturated fatty acids (PUFA)-derived lipid peroxides. Since depletion of GSH, inactivation of GPX4, altered iron metabolism, and upregulation of PUFA peroxidation by reactive oxygen species are peculiar signs of COVID-19, there is the possibility that SARS-CoV-2 may trigger ferroptosis in the cells of multiple organs, thus contributing to multiorgan damage. Here, we review the molecular mechanisms of ferroptosis and its possible relationship with SARS-CoV-2 infection and multiorgan damage. Finally, we analyze the potential interventions that may combat ferroptosis and, therefore, reduce multiorgan damage.
... Mechanistically, the reduced form of CoQ10 (CoQ10H 2 ) can successively trap two electrons, thereby preventing radical initiation as well as propagation of lipid peroxidation by scavenging lipid peroxyl radicals. A second function is to regenerate alpha-tocopherol from the tocopheroxyl radical, another important physiological lipid antioxidant [43]. Two independent studies found that the FSP1/CoQ10 system provides resistance to ferroptosis [44,45]. ...
Article
Full-text available
Ferroptosis is a regulated form of cell death characterized by iron dependency and increased lipid peroxidation. Initially assumed to be selectively induced in tumour cells, there is increasing evidence that ferroptosis plays an important role in pathophysiology and numerous cell types and tissues. Deregulated ferroptosis has been linked to human diseases, such as neurodegenerative diseases, cardiovascular disorders, and cancer. Along these lines, ferroptosis is a promising pathway to overcoming therapy resistance of cancer cells. It is therefore of utmost importance to understand the cellular signalling pathways and the molecular mechanisms underlying ferroptosis regulation, including context-specific effects mediated by the neighbouring cells through cell–cell contacts. Here, we give an overview on the molecular events and machinery linked to ferroptosis induction and commitment. We further summarize and discuss current knowledge about the role of cell–cell contacts, which differ in ferroptosis regulation between normal somatic cells and cancer cells. We present emerging concepts on the underlying mechanisms, address open questions, and discuss the possible impact of cell–cell contacts on exploiting ferroptosis in cancer therapy.
... Thus, Coenzyme Q10 and Vitamin E and their combination were tested against arsenic-induced testicular oxidative stress and DNA damage in mouse blood cells. Coenzyme Q10 (CoQ10) is reported to work as a sturdy antioxidant, avoids the commencement and dissemination of lipid peroxidation in cellular bio-membranes, and supports rejuvenation of αtocopherol (10)(11)(12). The CoQ10 was reported to effectively protect testicular injury in mice induced by magnetic field radiation (13). ...
Research
Arsenic toxicity has become one of the major public health problems in certain parts of the world. Thus, it is rational to find out a suitable compound to prevent arsenic-induced toxicity for clinical usage. Hence, the Coenzyme Q10 and Vitamin E were tested against arsenic-induced testicular oxidative stress and DNA damage. The mice were divided into five groups, animals of the four groups were exposed to 136 ppm arsenic via drinking water for 30 days. Subsequently, animals of three groups were treated with Vitamin E (50 mg/kg b.wt.), Coenzyme Q10 (10 mg/kg b.wt.), and their combination for 30 days, and animals of the 4th group were maintained without antioxidant treatment. The animals of the 5 th group (without any treatment) served as control. Thereafter, blood was collected, for DNA damage study, and testis dissected out to assess oxidative stress. The body and testis weight gain was lower in the arsenic subjected group compared to the control group whereas antioxidants (Vitamin E, Coenzyme Q10, and combination) treatment checks to some extent this decline. Biochemical data indicated that lipid peroxidation level was higher while reduced glutathione, total thiol, superoxide dismutase, and total protein level was significantly lesser in the arsenic exposed group compared to the control group, and antioxidants treatment diminished arsenic-induced these alterations to some extent. Arsenic induces DNA damage in the blood cells of mice by displaying a significantly lower head DNA percentage and a higher level of tail DNA percentage, tail length, tail moment, while Vitamin E, Coenzyme Q10, and combination were able to lower these changes. The data further revealed that the combined treatment of Vitamin E, Coenzyme Q10 is more effective than the treatment of these antioxidants individually.
... Coenzyme Q10 (CoQ10) is a benzoquinone which is lipid-soluble and is being involved in the respiratory chain of mitochondria for ATP production [7]. CoQ10 is a good antioxidant because it has the ability to maintain continuous cycles of oxidation-reduction [8]. Many recent studies concluded that CoQ10 supplementation improves endocrine and metabolic functions of PCOS patients [9,10]. ...
Article
Full-text available
Background Clomiphene Citrate is considered the gold-standard for induction of ovulation and has been used for several years to treat PCOS related infertility. Unfortunately, 15-40% of women with PCOS are resistant to Clomiphene Citrate. The study aimed to evaluate potential benefits of adding the active form of Coenzyme Q10 (Ubiquinol) to Clomiphene Citrate compared with Human Menopausal Gonadotropins (hMG) in Clomiphene Citrate resistant PCOS patients. 148 PCOS Patients with Clomiphene Citrate resistance were randomized into two groups (A and B). In group A, controlled ovarian stimulation was done by Clomiphene Citrate 150 mg daily (from 2nd till 6th day of cycle) together with Ubiquinol starting from 2nd day till day of hCG triggering in a dose of 100 mg orally once daily. In group B, hMG was given from 2nd day of the cycle in a dose ranging from 75 to 225 IU. Serial transvaginal ultrasonography was done starting on cycle day 8 and continued till size of leading follicle reaches 18 mm or more then ovulation triggering was done. Thereafter, patients were advised for a timed intercourse (TI) after 36 hours. A blood sample was withdrawn seven days after hCG triggering, for measurement of serum progesterone. If the Patient presented with a missed period for one week, a serum sample was sent for β-hCG. Results There were no statistically significant differences (P > 0.05) between studied groups regarding; number of cases reaching mature follicular size, number of stimulated cycles, endometrial thickness on the day of hCG triggering, mid-luteal serum progesterone, positive serum pregnancy test and clinical pregnancy rate. Conclusions Addition of Ubiquinol to Clomiphene Citrate improved ovarian responsiveness in Clomiphene Citrate resistant patients with results comparable to conventional hMG stimulation protocol.
... Within the ETC, CoQ10 accepts electrons from complex I and II and transports them to complex III. Besides its critical role in the ETC, CoQ10 acts as a potential anti-inflammatory agent [131]. Preclinical data has already provided valuable information that supports the pathophysiological role of CoQ10 in patients with heart failure and ischemic heart disease. ...
Article
Full-text available
Atrial fibrillation (AF) is the most prevalent and progressive cardiac arrhythmia worldwide and is associated with serious complications such as heart failure and ischemic stroke. Current treatment modalities attenuate AF symptoms and are only moderately effective in halting the arrhythmia. Therefore, there is an urgent need to dissect molecular mechanisms that drive AF. As AF is characterized by a rapid atrial activation rate, which requires a high energy metabolism, a role of mitochondrial dysfunction in AF pathophysiology is plausible. It is well known that mitochondria play a central role in cardiomyocyte function, as they produce energy to support the mechanical and electrical function of the heart. Details on the molecular mechanisms underlying mitochondrial dysfunction are increasingly being uncovered as a contributing factor in the loss of cardiomyocyte function and AF. Considering the high prevalence of AF, investigating the role of mitochondrial impairment in AF may guide the path towards new therapeutic and diagnostic targets. In this review, the latest evidence on the role of mitochondria dysfunction in AF is presented. We highlight the key modulators of mitochondrial dysfunction that drive AF and discuss whether they represent potential targets for therapeutic interventions and diagnostics in clinical AF.
... C oQ is synthesized in mitochondria, where it functions as an essential cofactor in multiple processes including oxidative phosphorylation, fatty acid oxidation, and nucleotide biosynthesis [1][2][3] . CoQ is also present in membranes throughout the cell 4 , suggesting that it has a more widespread cellular importance than is currently appreciated. Recently, one such role for extramitochondrial CoQ in mammalian cells was identified with the discovery that plasma membrane-localized FSP1 exhibits CoQ-dependent activity in mitigating ferroptosis 5,6 , a form of regulated cell death caused by aberrant iron-dependent lipid peroxidation. ...
Article
Full-text available
Beyond its role in mitochondrial bioenergetics, Coenzyme Q (CoQ, ubiquinone) serves as a key membrane-embedded antioxidant throughout the cell. However, how CoQ is mobilized from its site of synthesis on the inner mitochondrial membrane to other sites of action remains a longstanding mystery. Here, using a combination of Saccharomyces cerevisiae genetics, biochemical fractionation, and lipid profiling, we identify two highly conserved but poorly characterized mitochondrial proteins, Ypl109c (Cqd1) and Ylr253w (Cqd2), that reciprocally affect this process. Loss of Cqd1 skews cellular CoQ distribution away from mitochondria, resulting in markedly enhanced resistance to oxidative stress caused by exogenous polyunsaturated fatty acids, whereas loss of Cqd2 promotes the opposite effects. The activities of both proteins rely on their atypical kinase/ATPase domains, which they share with Coq8—an essential auxiliary protein for CoQ biosynthesis. Overall, our results reveal protein machinery central to CoQ trafficking in yeast and lend insights into the broader interplay between mitochondria and the rest of the cell.
... Mitochondrial function also relies on membrane stability, mainly dependent on cardiolipin and coenzyme Q10 [138,139]. Elamipretide, a cardiolipin-stabilizer, has been first tested on a canine model of HF showing improvements in LVEF and reduction in circulating levels of NT-proBNP, tumor necrosis factor-and C-reactive Content courtesy of Springer Nature, terms of use apply. Rights reserved. ...
Article
Full-text available
After initial strategies targeting inotropism and congestion, the neurohormonal interpretative model of heart failure (HF) pathophysiology has set the basis for current pharmacological management of HF, as most of guideline recommended drug classes, including beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists, blunt the activation of detrimental neurohormonal axes, namely sympathetic and renin–angiotensin–aldosterone (RAAS) systems. More recently, sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, combining inhibition of RAAS and potentiation of the counter-regulatory natriuretic peptide system, has been consistently demonstrated to reduce mortality and HF-related hospitalization. A number of novel pharmacological approaches have been tested during the latest years, leading to mixed results. Among them, drugs acting directly at a second messenger level, such as the soluble guanylate cyclase stimulator vericiguat, or other addressing myocardial energetics and mitochondrial function, such as elamipretide or omecamtiv-mecarbil, will likely change the therapeutic management of patients with HF. Sodium glucose cotransporter 2 inhibitors, initially designed for the management of type 2 diabetes mellitus, have been recently demonstrated to improve outcome in HF, although mechanisms of their action on cardiovascular system are yet to be elucidated. Most of these emerging approaches have shifted the therapeutic target from neurohormonal systems to the heart, by improving cardiac contractility, metabolism, fibrosis, inflammation, and remodeling. In the present paper, we review from a pathophysiological perspective current and novel therapeutic strategies in chronic HF.
... Reflecting such core functions, genetic defects that fully block ubiquinone biosynthesis in plants result in embryo lethal phenotypes (3,4). Because ubiquinone is one of the major liposoluble free-radical scavengers in eukaryotes (1,5), there has been sustained interest in engineering crops with higher ubiquinone content in order to enhance their nutritional value and improve their resistance to abiotic stresses (6)(7)(8)(9)(10). This engineering approach, however, is contingent upon the knowledge of the ubiquinone biosynthetic pathway and its regulation in plants. ...
Article
Full-text available
Ubiquinone (Coenzyme Q) is a vital respiratory cofactor and liposolubule antioxidant. In plants, it is not known how the C-6 hydroxylation of demethoxyubiquinone, the penultimate step in ubiquinone biosynthesis, is catalyzed. The combination of cross-species gene network modeling along with mining of embryo-defective mutant databases of Arabidopsis thaliana identified the embryo lethal locus EMB2421 (At1g24340) as a top candidate for the missing plant demethoxyubiquinone hydroxylase. In marked contrast with prototypical eukaryotic demethoxyubiquinone hydroxylases, the catalytic mechanism of which depends on a carboxylate-bridged di-iron domain, At1g24340 is homologous to FAD-dependent oxidoreductases that instead use NAD(P)H as an electron donor. Complementation assays in Saccharomyces cerevisiae and Escherichia coli demonstrated that At1g24340 encodes a functional demethoxyubiquinone hydroxylase and that the enzyme displays strict specificity for the C-6 position of the benzoquinone ring. Laser-scanning confocal microscopy also showed that GFP-tagged At1g24340 is targeted to mitochondria. Silencing of At1g24340 resulted in 40-74% decrease in ubiquinone content and de novo ubiquinone biosynthesis. Consistent with the role of At1g24340 as a benzenoid ring modification enzyme, this metabolic blockage could not be bypassed by supplementation with 4-hydroxybenzoate, the immediate precursor of ubiquinone's ring. Unlike in yeast, in Arabidopsis overexpression of demethoxyubiquinone hydroxylase did not boost ubiquinone content. Phylogenetic reconstructions indicated that plant demethoxyubiquinone hydroxylase is most closely related to prokaryotic monooxygenases that act on halogenated aromatics, and likely descends from an event of horizontal gene transfer between a green alga and a bacterium.
... CoQ10 facilitates electron transfer from complex I (NADH coenzyme Q reductase) to complex III (cytochrome bc1 complex), and from complex II (succinate dehydrogenase) to complex III [58,59]. It may also stabilize the mitochondrial permeability transition pore and reduce apoptotic cell loss [58]. ...
Article
Full-text available
Heart failure is a devastating clinical syndrome, but current therapies are unable to abolish the disease burden. New strategies to treat or prevent heart failure are urgently needed. Over the past decades, a clear relationship has been established between poor cardiac performance and metabolic perturbations, including deficits in substrate uptake and utilization, reduction in mitochondrial oxidative phosphorylation and excessive reactive oxygen species production. Together, these perturbations result in progressive depletion of cardiac adenosine triphosphate (ATP) and cardiac energy deprivation. Increasing the delivery of energy substrates (e.g., fatty acids, glucose, ketones) to the mitochondria will be worthless if the mitochondria are unable to turn these energy substrates into fuel. Micronutrients (including coenzyme Q10, zinc, copper, selenium and iron) are required to efficiently convert macronutrients to ATP. However, up to 50% of patients with heart failure are deficient in one or more micronutrients in cross‐sectional studies. Micronutrient deficiency has a high impact on mitochondrial energy production and should be considered an additional factor in the heart failure equation, moving our view of the failing myocardium away from an “an engine out of fuel” to “a defective engine on a path to self‐destruction.” This summary of evidence suggests that supplementation with micronutrients—preferably as a package rather than singly—might be a potential therapeutic strategy in the treatment of heart failure patients.
... Another interesting compound is CoQ10. This is an electron carrier in mitochondrial electron-transport chain [225] and an efficient liposoluble antioxidant [226]. These two CoQ10 properties are beneficial for mitochondrial bioenergetics [227]. ...
Article
Full-text available
Muscular dystrophies (MDs) are a heterogeneous group of congenital neuromuscular disorders whose clinical signs include myalgia, skeletal muscle weakness, hypotonia, and atrophy that leads to progressive muscle disability and loss of ambulation. MDs can also affect cardiac and respiratory muscles, impairing life-expectancy. MDs in clude Duchenne muscular dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy and limb-girdle muscular dystrophy. These and other MDs are caused by mutations in genes that encode proteins responsible for the structure and function of skeletal muscles, such as components of the dystrophin-glycoprotein-complex that connect the sarcomeric-actin with the extracellular matrix, allowing contractile force transmission and providing stability during muscle contraction. Consequently, in dystrophic conditions in which such proteins are affected, muscle integrity is disrupted, leading to local inflammatory responses, oxidative stress, Ca2+-dyshomeostasis and muscle degeneration. In this scenario, dysregulation of connexin hemichannels seem to be an early disruptor of the homeostasis that further plays a relevant role in these processes. The interaction between all these elements constitutes a positive feedback loop that contributes to the worsening of the diseases. Thus, we discuss here the interplay between inflammation, oxidative stress and connexin hemichannels in the progression of MDs and their potential as therapeutic targets.
... Coenzyme Q10 (CoQ10) or ubiquinone-10 is a part of the respiratory chain complex, which also has antioxidant activity as it prevents electron leakage in mitochondria that results in ROS production (Hernández-Camacho et al., 2018). CoQ10 in its reduced form of Ubiquinol oxidizes free radicals and decreases their levels in the aged cell (Bentinger et al., 2007). As CoQ10 is water-insoluble, its addition via nano-particle to bovine in-vitro culture media has shown to improve cleavage rate, blastocyst development, and cell numbers (Stojkovic et al., 1999). ...
Article
Full-text available
Culture media has an important role in invitro embryo development and in determining the success rate of assisted reproduction technologies. Extensive research during the last few decades have brought about major advancements in the IVF culture media. Studies on the composition of the mammlian oviductal fluids and the uterine fluids have improved our understanding on the evolving metabolic needs of the preimplantation embryo. This has led to the gradual development of human IVF media, from simple salt solutions to highly complex defined media. Regarding ideal composition of IVF culture media two different philosophies have come up: “back-to-nature” or sequential culture principle and “let-the-embryo-choose” or one-step culture principle. Sequential culture closely mimics the physiological conditions of female reproductive tract, while the mono culture system employs simultaneous use of all components in an optimal concentration. Besides role in viability maintenance, culture media can also take up a new role as a therapeutic agent in future. The improvised media apart from maintaining the viability may work on improving the quality of gametes/embryos obtained from poor prognosis patients. This review would discuss the progressive evolution of embryo culture media based on studies on pre-implantation embryo physiology and lastly will hypothesize the future of this technology.
... The CoQ10 can be used as a free radical collecting antioxidant (RTA) to capture the oxygen free radicals in the cell membrane and further prevent the peroxidation of phospholipids in the cell membrane ( Figure 3). The FPS1/CoQ10 system is parallel to GPX4 and System Xc, maintaining cell redox balance (Takahashi et al., 1993;Bentinger et al., 2007) ...
Article
Full-text available
The occurrence and development of tumors involve a series of life activities of cells, among which cell death has always been a crucial part in the research of tumor mechanisms and treatment methods. Ferroptosis is a non-apoptotic form of cell death, which is characterized by lipid peroxidation accumulation and further cell membrane rupture caused by excessive production of intracellular oxygen free radicals dependent on iron ions. Esophageal cancer is one of the common digestive tract tumors. Patients in the early stage are mainly treated with surgery, and the curative effect is awe-inspiring. However, surgery is far from enough for terminal patients, and it is the best choice to combine radiotherapy and chemotherapy before the operation or during the perioperative period. Although the treatment plan for patients with advanced esophageal cancer is constantly being optimized, we are disappointed at the still meager 5-year survival rate of patients and the poor quality of life. A series of complex problems, such as increased chemotherapy drug resistance and decreased radiotherapy sensitivity of esophageal cancer cells, are waiting for us to tackle. Perhaps ferroptosis can provide practical and feasible solutions and bring new hope to patients with advanced esophageal cancer. The occurrence of ferroptosis is related to the dysregulation of iron metabolism, lipid metabolism, and glutamate metabolism. Therefore, these dysregulated metabolic participant proteins and signaling pathways are essential entry points for using cellular ferroptosis to resist the occurrence and development of cancer cells. This review first introduced the main regulatory mechanisms of ferroptosis. It then summarized the current research status of ferroptosis in esophageal cancer, expecting to provide ideas for the research related to ferroptosis in esophageal cancer.
... CoQ10 is critical for electron transfer in the mitochondrial membrane for respiratory chain activity. In addition, when reduced, it forms CoQH 2 , which also acts as a lipophilic freeradical-trapping antioxidant (RTA) in the plasma membrane [69], thereby suppressing lipid peroxidation and ferroptosis. It has also been suggested that FSP1 can be used as a biomarker of resistance to ferroptosis. ...
Article
Full-text available
Ferroptosis has recently been demonstrated to be a novel regulated non-apoptotic cell death characterized by iron-dependence and the accumulation of lipid peroxidation that results in membrane damage. Excessive iron induces ferroptosis by promoting the generation of both soluble and lipid ROS via an iron-dependent Fenton reaction and lipoxygenase (LOX) enzyme activity. Cytosolic glutathione peroxidase 4 (cGPX4) pairing with ferroptosis suppressor protein 1 (FSP1) and mitochondrial glutathione peroxidase 4 (mGPX4) pairing with dihydroorotate dehydrogenase (DHODH) serve as two separate defense systems to detoxify lipid peroxidation in the cytoplasmic as well as the mitochondrial membrane, thereby defending against ferroptosis in cells under normal conditions. However, disruption of these defense systems may cause ferroptosis. Emerging evidence has revealed that ferroptosis plays an essential role in the development of diverse cardiovascular diseases (CVDs), such as hemochromatosis-associated cardiomyopathy, doxorubicin-induced cardiotoxicity, ischemia/reperfusion (I/R) injury, heart failure (HF), atherosclerosis, and COVID-19–related arrhythmias. Iron chelators, antioxidants, ferroptosis inhibitors, and genetic manipulations may alleviate the aforementioned CVDs by blocking ferroptosis pathways. In conclusion, ferroptosis plays a critical role in the pathogenesis of various CVDs and suppression of cardiac ferroptosis is expected to become a potential therapeutic option. Here, we provide a comprehensive review on the molecular mechanisms involved in ferroptosis and its implications in cardiovascular disease.
... For example, "pyruvate fermentation to butanoate", menaquinol biosynthesis, and ubiquinol biosynthesis were enriched after prebiotics treatments. Menaquinone is vitamin K2, which plays an important role in hepatic coagulation [4], and ubiquinol is a reduced form of coenzyme Q10, which acts as electron carrier in cellular respiration and thus works as an antioxidant [49,50]. ...
Article
Full-text available
Prebiotics are non-digestible food ingredients that promote the growth of beneficial gut microorganisms and foster their activities. The performance of prebiotics has often been tested in mouse models in which the gut ecology differs from that of humans. In this study, we instead performed an in vitro gastrointestinal digestion and fecal fermentation experiment to evaluate the efficiency of eight different prebiotics. Feces obtained from 11 different individuals were used to ferment digested prebiotics. The total DNA from each sample was extracted and sequenced through Illumina MiSeq for microbial community analysis. The amount of short-chain fatty acids was assessed through gas chromatography. We found links between community shifts and the increased amount of short-chain fatty acids after prebiotics treatment. The results from differential abundance analysis showed increases in beneficial gut microorganisms, such as Bifidobacterium, Faeclibacterium, and Agathobacter, after prebiotics treatment. We were also able to construct well-performing machine-learning models that could predict the amount of short-chain fatty acids based on the gut microbial community structure. Finally, we provide an idea for further implementation of machine-learning techniques to find customized prebiotics.
... CoQ10 is a naturally found in dietary sources and a dietary supplement. It is present in a wide variety of foods from animal and vegetable sources, with large amounts present in chicken legs, heart, liver, and herrings; and in vegetables such as spinach and cauliflower; and whole grains but in a lower concentration in comparison with meat and fish (99) . is effective in preventing not only lipid peroxidation but also protein oxidation by quenching the initiating perferryl radical and functioning as a chain-breaking antioxidant, thus preventing propagation (101) . Chapter Two Materials and Methods ...
Thesis
Full-text available
Declaration Hereby I declare that the present thesis is exclusively my own work, based on my research in the department of clinical biochemistry at
... CoQ10 can be metabolized in all tissues by phosphorylation in the cells and then transportation to the kidneys. CoQ10 is frequently found in cell membranes, particularly in mitochondria [30]. CoQ10 exerts its biological effect largely on the basis of its lipophilic antioxidant capacity, scavenging free radicals by suppressing the initiation and development of lipid peroxidation in cell membranes [31]. ...
Article
Full-text available
Coenzyme Q10 (CoQ10), an endogenous antioxidant, has been reported frequently to exert an outstanding protective effect on multiple organ injury, including acute kidney injury (AKI). In this study, we aim to summarize all the current evidence of the protective action of CoQ10 against AKI as there are presently no relevant reviews in the literature. After a systematic search, 20 eligible studies, either clinical trials or experimental studies, were included and further reviewed. CoQ10 treatment exhibited a potent renal protective effect on various types of AKI, such as AKI induced by drugs (e.g., ochratoxin A, cisplatin, gentamicin, L-NAME, and nonsteroidal anti-inflammatory drug), extracorporeal shock wave lithotripsy (ESWL), sepsis, contrast media, and ischemia–reperfusion injury. The renal protective role of CoQ10 against AKI might be mediated by the antiperoxidative, anti-apoptotic, and anti-inflammatory potential of CoQ10. The molecular mechanisms for the protective effects of CoQ10 might be attributed to the regulation of multiple essential genes (e.g., caspase-3, p53, and PON1) and signaling cascades (e.g., Nrf2/HO-1 pathway). This review highlights that CoQ10 may be a potential strategy in the treatment of AKI.
... CoQ10 has been reported to have an important role in various clinical aspects. It is known to affect mitochondrial conditions and neurodegenerative, diabetes, cardiovascular, male infertility, and few other diseases (Bentinger et al., 2007;Quinzii and Hirano, 2010). A fermented fish called Jeotgal contained the highest content of CoQ9 (315.9 μg/g of fermented fish), which was significantly higher than raw fish (Pyo and Oh, 2011). ...
Chapter
Fermented fish and other aquatic fermented products are unique in terms of nutritional value and sensory attributes, thereby holding a high demand around the globe. Based on the geological significance, Southeast Asia dominates various traditional fermented fish products compared to European countries owing to the availability of a wide range of raw materials. Generally, fermentation is known to have an important role in preserving nutrients, improving textural and flavor properties of fish. Primarily, this could depend on the types of fermentation methods (spontaneous and non-spontaneous) and quality of raw material employed. During fermentation, the enzyme activity influenced by the interaction of various native or selective microflora has been correlated to generate diversified bioactive compounds. Some of these compounds are known to exhibit numerous health benefits and are termed “bioactive compounds.” In addition, these bioactive compounds are known to show a protective or preventive role against various diseases. Concerning this, the present chapter aims to provide information on fermented fish and other aquatic fermented products based on the geographic distribution, their traditional significance and types of fermentation processes, microbiome involved, bioactive compounds pertaining fermentation process, and various health benefits such as antioxidant, antidiabetic, anticancer properties, etc.
... In addition, it feeds electrons into the respiratory chain from other entry points, including the electron transfer flavoprotein, sulfide-quinone reductase, and dihydroorotate dehydrogenase [1][2][3][4]. CoQ10 is known to have antioxidant properties and to be involved in several other cellular functions outside of mitochondria [5,6]. As far as is known, all cells rely exclusively on endogenous CoQ synthesis. ...
Preprint
Coenzyme Q 10 (CoQ 10 ) is necessary for mitochondrial electron transport. Mutations in CoQ 10 biosynthetic genes cause primary CoQ 10 deficiency (PCoQD) and manifest as mitochondrial disorders. It is often stated that PCoQD patients can be treated by oral CoQ 10 supplementation. To test this, we compiled all studies describing PCoQD patients up to May 2022. We excluded studies with no data on CoQ 10 treatment, or with insufficient description of effectiveness. Out of 303 PCoQD patients identified, we retained 89 cases, of which 24 reported improvements after CoQ 10 treatment (27.0%). In five cases, the patient’s condition was reported to deteriorate after halting of CoQ 10 treatment. 12 cases reported improvement in the severity of ataxia, and 5 cases in the severity of proteinuria. Only a subjective description of improvement was reported for four patients described as responding. All reported responses were partial improvements of only some symptoms. For PCoQD patients, CoQ 10 supplementation is replacement therapy. Yet, there is only very weak evidence for the efficacy of the treatment. Our findings thus suggest a need for caution when seeking to justify the widespread use of CoQ 10 for the treatment of any disease or as dietary supplement. Highlights Only 27% of primary CoQ 10 deficiency patients benefited from CoQ 10 supplementation. Studies of the effects of supplementation necessarily lacked controls and blinding. All reported positive responses to treatment only partially improved few symptoms. CoQ 10 supplementation for the treatment of any disease should be questioned. Firm evidence of benefits requires randomize, controlled trials of CoQ 10 therapy. Graphic Abstract
... Human Coenzyme Q10 monooxygenase 6 (COQ6) is a flavoprotein involved in the biosynthesis of Coenzyme Q10 which operates as a redox carrier by transferring electrons from respiratory chain Complexes I and II to Complex III. Coenzyme Q10 is also a potent antioxidant [62] and a cofactor of many mitochondrial dehydrogenases. It is required for pyrimidine nucleoside biosynthesis and has been implicated in the inhibition of apoptosis by preventing the collapse of the inner mitochondrial membrane [63] . ...
Article
Full-text available
Riboflavin, known as vitamin B2, a water-soluble vitamin, is an essential nutrient in vertebrates, hence adequate dietary intake is imperative. Riboflavin plays a role in a variety of metabolic pathways, serving primarily as an integral component of its crucial biologically active forms, the flavocoenzymes flavin adenine dinucleotide and flavin mononucleotide. These flavocoenzymes ensure the functionality of numerous flavoproteins including dehydrogenases, oxidases, monooxygenases, and reductases, which play pivotal roles in mitochondrial electron transport chain, β-oxidation of fatty acids, redox homeostasis, citric acid cycle, branched-chain amino acid catabolism, chromatin remodeling, DNA repair, protein folding, and apoptosis. Unsurprisingly, impairment of flavin homeostasis in humans has been linked to various diseases including neuromuscular and neurological disorders, abnormal fetal development, and cardiovascular diseases. This review presents an overview of riboflavin metabolism, its role in mitochondrial function, primary and secondary flavocoenzyme defects associated with mitochondrial dysfunction, and the role of riboflavin supplementation in these conditions.
... As most cellular functions depend on an adequate supply of ATP, CoQ10 is essential for the health of virtually all human tissues and organs. The concentration of CoQ10 in an organ depends on its energy needs or metabolic activity; therefore, tissues with high concentrations of this compound include the heart, the kidney, the liver, and muscles [10]. ...
Article
Full-text available
Introduction: Diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) have become some of the most urgent and prevalent health problems in recent decades, side by side with the growing obesity crisis. The intimate relationship between T2DM and CVD has become clear: endothelial dysfunction caused by oxidative stress and inflammation resulting from hyperglycaemia is the key factor in the development of vascular complications of T2DM, leading to CVD. Coenzyme Q10 (CoQ10) is a great candidate for the treatment of these diseases, acting precisely at the intersection between T2DM and CVD: oxidative stress, due to its strong antioxidant activity and fundamental physiological role in mitochondrial bioenergetics. CoQ10 is a biologically active liposoluble compound comprising a quinone group and a side chain of 10 isoprenoid units, which is synthesized endogenously in the body from tyrosine and mevalonic acid. The main biochemical action of CoQ10 is as a cofactor in the electron transport chain that synthesizes adenosine triphosphate (ATP). As most cellular functions depend on an adequate supply of ATP, CoQ10 is essential for the health of virtually all human tissues and organs. CoQ10 supplementation has been used as an intensifier of mitochondrial function and an antioxidant with the aim of palliating or reducing oxidative damage that can worsen the physiological outcome of a wide range of diseases including T2DM and CVDs. Conclusion: Although there is not enough evidence to conclude it is effective for different therapeutic indications, CoQ10 supplementation is probably safe and well tolerated, with few drug interactions and minor side effects. Many valuable advances have been made on the use of CoQ10 in clinical practice for patients with T2DM and a high risk of CVD. However, further research is needed to assess the real safety and benefit to indicate CoQ10 supplementation in patients with T2DM.
... Phytol kinase activity requires phosphate donors such as ATP, CTP, UTP, or GTP. In most organisms, various isoprenoid phosphorylation reactions are mediated by CTP (Heller et al., 1992;Inoue et al., 1994;Bentinger et al., 2007). ...
Article
Full-text available
Malaria is one of the most widespread parasitic diseases, especially in Africa, Southeast Asia and South America. One of the greatest problems for control of the disease is the emergence of drug resistance, which leads to a need for the development of new antimalarial compounds. The biosynthesis of isoprenoids has been investigated as part of a strategy to identify new targets to obtain new antimalarial drugs. Several isoprenoid quinones, including menaquinone-4 (MK-4/vitamin K2), α- and γ-tocopherol and ubiquinone (UQ) homologs UQ-8 and UQ-9, were previously detected in in vitro cultures of Plasmodium falciparum in asexual stages. Herein, we described for the first time the presence of phylloquinone (PK/vitamin K1) in P. falciparum and discuss the possible origins of this prenylquinone. While our results in metabolic labeling experiments suggest a biosynthesis of PK prenylation via phytyl pyrophosphate (phytyl-PP) with phytol being phosphorylated, on the other hand, exogenous PK attenuated atovaquone effects on parasitic growth and respiration, showing that this metabolite can be transported from extracellular environment and that the mitochondrial electron transport system (ETS) of P. falciparum is capable to interact with PK. Although the natural role and origin of PK remains elusive, this work highlights the PK importance in plasmodial metabolism and future studies will be important to elucidate in seeking new targets for antimalarial drugs.
... CoQ 10 (ubiquinone) is best known as a component of the ETC. CoQ 10 can also function as an antioxidant [126]. In a rat model of preeclampsia induced by N ω -Nitro-l-arginine-methyl ester (l-NAME), CoQ 10 reduces systolic blood pressure, proteinuria, and increases birth weight along with increased mitochondrial membrane potential and mtDNA [127]. ...
Article
Full-text available
Purpose of Review Preeclampsia complicates 5–10% of all pregnancies and is a leading cause of maternal and perinatal mortality and morbidity. The placenta plays a pivotal role in determining pregnancy outcome by supplying the fetus with oxygen and nutrients and by synthesizing hormones. Placental function is highly dependent on energy supplied by mitochondria. It is well-known that preeclampsia is originated from placental dysfunction, although the etiology of it remains elusive. Recent Findings During the last three decades, substantial evidence suggests that mitochondrial abnormality is a major contributor to placental dysfunction. In addition, mitochondrial damage caused by circulating bioactive factors released from the placenta may cause endothelial dysfunction and subsequent elevation in maternal blood pressure. Summary In this review, we summarize the current knowledge of mitochondrial abnormality in the pathogenesis of preeclampsia and discuss therapeutic approaches targeting mitochondria for treatment of preeclampsia.
Article
Hyperoxia, is often used in preterm supportive care, leading to high oxygen exposure in neonates. Coenzyme Q10 (CoQ10) is a free radical scavenger that has been studied in older children but never be investigated for its role in preterm care. We hypothesize that the administration of exogenous CoQ10 would raise serum concentrations of CoQ10 and mitigate the adverse effects of hyperoxia on the organs by reducing oxygen‐free radicals and inflammation. The aim of this study was to evaluate the effects of oxidative stress, inflammatory response, and survival in neonatal rats after CoQ10 treatment. Neonatal rats delivered from four pregnant Wistar rats were randomly divided into four groups: (a) control, (b) CoQ10, (c) hyperoxia (O2 group), and (d) treatment (CoQ10 + O2) groups. The dose of CoQ10 injected was 30 mg/kg. The CoQ9, CoQ10, cytokines, oxidative stress, and antioxidant enzyme activity were measured. Tissue samples were histologically examined and mortality was monitored for 16 days. The level of CoQ9 significantly increased in the liver, kidney, and plasma, while the level of CoQ10 significantly increased in most organ tissues in the CoQ10 + O2 group. Additionally, CoQ10 decrease oxidative stress in the liver, increase antioxidant enzyme activity in the heart, kidney, and brain, and reverse an inclined level of hematopoietic growth factors. However, CoQ10 had no effect on inflammation, organ damage, or mortality. Therefore, the use of CoQ10 in potential adjuvant therapy for neonatal hyperoxia requires further research.
Thesis
L’ubiquinone, ou coenzyme Q (CoQ ou UQ), est un lipide polyprénylé qui joue un rôle important dans le transport des électrons dans les chaînes respiratoires chez E. coli. La biosynthèse de l'UQ en aérobie chez E. coli nécessite huit réactions et implique au moins douze protéines (UbiA-UbiK et UbiX). Dans ce travail, nous démontrons que les protéines Ubi forment le complexe Ubi, un métabolon stable qui catalyse les six dernières réactions de la voie de biosynthèse. La structure tridimensionnelle du domaine SCP2 d’UbiJ forme une cavité hydrophobe étendue qui lie les intermédiaires de l’UQ à l'intérieur du complexe d’1-MDa. Le complexe Ubi est purifié à partir des extraits cytoplasmiques et la biosynthèse de l'UQ a lieu dans cette fraction, remettant en question l’hypothèse actuelle d'un processus de biosynthèse associé à la membrane. L’UQ est connue pour être synthétisée en aérobie et anaérobie. Nous caractérisons une nouvelle voie de biosynthèse de l’UQ indépendante de l'O2. Cette voie repose sur trois protéines, UbiT, UbiU et UbiV. UbiT possède un domaine de liaison aux lipides SCP2 et est probablement un facteur accessoire de la voie de biosynthèse, tandis qu’UbiU et UbiV (UbiU-UbiV) sont impliqués dans les réactions d'hydroxylation et représentent une nouvelle classe d'hydroxylases indépendantes de l’O2. Nous démontrons qu’UbiU-UbiV d’E.coli forme un hétérodimère, chaque protéine se lie à un centre [4Fe-4S] via des cystéines conservées essentielles à l'activité. De plus, nous montrons qu’UbiU purifié de P. aeruginosa est capable de lier de l’UQ, suggérant un rôle différent d’UbiU et d’UbiV. UbiU et UbiV appartiennent à la famille des peptidases U32, dont la fonction reste discutable. Nous démontrons, par des analyses bioinformatiques, que les protéines U32 sont caractérisées par quatre cystéines conservées très importantes pour leurs activités enzymatiques et par des outils biochimiques, nous confirmons que RlhA et TrhP, deux autres protéines de la famille U32, comme UbiU et UbiV, sont des protéines Fe-S.
Article
Full-text available
Aiming to understand the effects of CoQ10 dietary supplementation on growth performance, feed utilisation, and immune response in Macrobrachium rosenbergii and Micropterus salmoides largemouth bass M.rosenbergii, weighing 3.69±0.92 g, was fed four experimental diets containing CoQ10 at concentrations of 0, 25, 50, and 100 mg kg1 (C, R, Y, and Z, respectively). On M. rosenbergii, there was no significant difference in WG, SGR, FI, or SR. Body composition did not differ in terms of Moisture, protein, fat, or ash (P>0.05). The activities of Lipase, Trypsin, and Amylase did not alter (P>0.05). The activities of SOD, MDA, and Lysozyme in prawn hemolymph did not alter in any of the diets (P>0.05). However, the group given 25mg/kg CoQ10 had considerably higher ACP activity (P<0.05). In conclusion, CoenzymeQ10 has no effect on Macrobachium rosenbergii growth. The results revealed that 25mg/kg CoQ10 could increase immunity and digestive enzyme performance in M. rosenbergii freshwater prawns. Introduction:
Article
Ubiquinone (coenzyme Q) is a vital respiratory cofactor and liposoluble antioxidant. Studies have shown that plants derive approximately a quarter of 4-hydroxybenzoate, which serves as the direct ring precursor of ubiquinone, from the catabolism of kaempferol. Biochemical and genetic evidence suggests that the release of 4-hydroxybenzoate from kaempferol is catalyzed by heme-dependent peroxidases and that 3-O-glycosylations of kaempferol act as a negative regulator of this process. These findings not only represent an atypical instance of primary metabolite being derived from specialized metabolism but also raise the question as to whether ubiquinone contributes to the ROS scavenging and signaling functions already established for flavonols.
Chapter
Coenzyme Q (CoQ) is a ubiquitous lipidic molecule located in all cell membranes and lipoproteins in blood plasma. Its phenolic head gives it the capacity to accept and donate electrons. For this reason, it is the main lipidic redox compound in cells. This property permits CoQ to take part in the mitochondrial electron transfer chain and in many other activities in mitochondria, and also to act as the major antioxidant in the lipid environment of the organism. During aging, the endogenous synthesis of CoQ decreases. Due to its central function, this decrease can affect many metabolic, signaling, and antioxidant activities, probably severely influencing aging progression. Further, CoQ depletion has been also associated with many aging-associated and metabolic diseases. This chapter revises the importance of this key molecule in cell physiology and aging progression.
Article
Full-text available
Coenzyme Q10 (CoQ10) is necessary for mitochondrial electron transport. Mutations in CoQ10 biosynthetic genes cause primary CoQ10 deficiency (PCoQD) and manifest as mitochondrial disorders. It is often stated that PCoQD patients can be treated by oral CoQ10 supplementation. To test this, we compiled all studies describing PCoQD patients up to May 2022. We excluded studies with no data on CoQ10 treatment, or with insufficient description of effectiveness. Out of 303 PCoQD patients identified, we retained 89 cases, of which 24 reported improvements after CoQ10 treatment (27.0%). In five cases, the patient's condition was reported to deteriorate after halting of CoQ10 treatment. 12 cases reported improvement in the severity of ataxia and 5 cases in the severity of proteinuria. Only a subjective description of improvement was reported for 4 patients described as responding. All reported responses were partial improvements of only some symptoms. For PCoQD patients, CoQ10 supplementation is replacement therapy. Yet, there is only very weak evidence for the efficacy of the treatment. Our findings, thus, suggest a need for caution when seeking to justify the widespread use of CoQ10 for the treatment of any disease or as dietary supplement.
Article
Full-text available
Background: Chronic heart failure is a debilitating condition that accounts for an annual NHS spend of £2.3B. Low levels of endogenous coenzyme Q10 may exacerbate chronic heart failure. Coenzyme Q10 supplements might improve symptoms and slow progression. As statins are thought to block the production of coenzyme Q10, supplementation might be particularly beneficial for patients taking statins. Objectives: To assess the clinical effectiveness and cost-effectiveness of coenzyme Q10 in managing chronic heart failure with a reduced ejection fraction. Methods: A systematic review that included randomised trials comparing coenzyme Q10 plus standard care with standard care alone in chronic heart failure. Trials restricted to chronic heart failure with a preserved ejection fraction were excluded. Databases including MEDLINE, EMBASE and CENTRAL were searched up to March 2020. Risk of bias was assessed using the Cochrane Risk of Bias tool (version 5.2). A planned individual participant data meta-analysis was not possible and meta-analyses were mostly based on aggregate data from publications. Potential effect modification was examined using meta-regression. A Markov model used treatment effects from the meta-analysis and baseline mortality and hospitalisation from an observational UK cohort. Costs were evaluated from an NHS and Personal Social Services perspective and expressed in Great British pounds at a 2019/20 price base. Outcomes were expressed in quality-adjusted life-years. Both costs and outcomes were discounted at a 3.5% annual rate. Results: A total of 26 trials, comprising 2250 participants, were included in the systematic review. Many trials were reported poorly and were rated as having a high or unclear risk of bias in at least one domain. Meta-analysis suggested a possible benefit of coenzyme Q10 on all-cause mortality (seven trials, 1371 participants; relative risk 0.68, 95% confidence interval 0.45 to 1.03). The results for short-term functional outcomes were more modest or unclear. There was no indication of increased adverse events with coenzyme Q10. Meta-regression found no evidence of treatment interaction with statins. The base-case cost-effectiveness analysis produced incremental costs of £4878, incremental quality-adjusted life-years of 1.34 and an incremental cost-effectiveness ratio of £3650. Probabilistic sensitivity analyses showed that at thresholds of £20,000 and £30,000 per quality-adjusted life-year coenzyme Q10 had a high probability (95.2% and 95.8%, respectively) of being more cost-effective than standard care alone. Scenario analyses in which the population and other model assumptions were varied all found coenzyme Q10 to be cost-effective. The expected value of perfect information suggested that a new trial could be valuable. Limitations: For most outcomes, data were available from few trials and different trials contributed to different outcomes. There were concerns about risk of bias and whether or not the results from included trials were applicable to a typical UK population. A lack of individual participant data meant that planned detailed analyses of effect modifiers were not possible. Conclusions: Available evidence suggested that, if prescribed, coenzyme Q10 has the potential to be clinically effective and cost-effective for heart failure with a reduced ejection fraction. However, given important concerns about risk of bias, plausibility of effect sizes and applicability of the evidence base, establishing whether or not coenzyme Q10 is genuinely effective in a typical UK population is important, particularly as coenzyme Q10 has not been subject to the scrutiny of drug-licensing processes. Stronger evidence is needed before considering its prescription in the NHS. Future work: A new independent, well-designed clinical trial of coenzyme Q10 in a typical UK heart failure with a reduced ejection fraction population may be warranted. Study registration: This study is registered as PROSPERO CRD42018106189. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 4. See the NIHR Journals Library website for further project information.
Article
In this study, (24) Awassi rams were used at the age of (1.5-2 years), with an average weight of (46.4 kg) to study the effect of giving some antioxidants on hematological and blood biochemical on Awassi rams , The rams were randomly allotted into four groups of equal number (6) rams each group , the first group (control) , the second group was given turmeric at the rate of 3 g / kg feed / head daily, the third group was supplemented orally with 400 IU vitamin E / head three times a week , the fourth group was supplemented orally with 400 mg CoQ10 coenzyme / head three times a week , and these materials were given to the rams of each treatment before providing the daily feed to the animals , The experimental animals were given a standardized diet consisting of ( concentrated feed + Wheat Straw ) on the basis of 2.5 % of live body weight . The percentage of protein in the diet was 15.22% and the metabolic energy was (2721.5) kcal / kg of feed. The weights of the animals were measured and blood samples were drawn from the jugular vein every month to measure the characteristics of the physical and biochemical parameters of the blood in the blood serum. The results of the study showed a significant (p?0.01) effect of the treatments on the characteristics of the animal’s weight, number of WBC, the percentage of eosinophil's and basophils than control group , while the treatments did not show a significant effect on the other blood values. The results also showed a significant effect of the treatments on the level of concentration of total protein, cholesterol, triglycerides, globulin and urea, in addition to the levels of HDL, LDL , While there was no significant effect of the treatments on the concentration of glucose, albumin, VLDL in the blood plasma. Through the results of this study, we conclude that giving antioxidants to rams had a positive effect on some physical, biochemical and enzymatic parameters of blood in the treated groups compared to the control.
Preprint
Full-text available
Herbicide resistance in weeds is a growing threat to global crop production. Non-target site resistance is problematic because a single resistance allele can confer tolerance to many herbicides (cross resistance), and it is often a polygenic trait so it can be difficult to identify the molecular mechanisms involved. Most characterized molecular mechanisms of non-target site resistance are caused by gain-of-function mutations in genes from a few key gene families – the mechanisms of resistance caused by loss-of-function mutations remain unclear. In this study, we first show that the mechanism of non-target site resistance to the herbicide thaxtomin A conferred by loss-of-function of the gene PAM16 is conserved in Marchantia polymorpha , validating its use as a model species with which to study non-target site resistance. To identify mechanisms of non-target site resistance caused by loss-of-function mutations, we generated 10 ⁷ UV-B mutagenized M. polymorpha spores and screened for resistance to the herbicide thaxtomin A. We isolated 13 thaxtomin A-resistant mutants and found that 3 mutants carried candidate resistance-conferring SNPs in the Mp RTN4IP1L gene. Mp rtn4ip1l mutants are defective in coenzyme Q biosynthesis and accumulate higher levels of reactive oxygen species (ROS) than wild-type plants. Mutants are also defective in thaxtomin A metabolism, consistent with the hypothesis that loss of Mp RTN4IP1L function confers non-target site resistance. We conclude that loss of Mp RTN4IP1L function is a novel mechanism of non-target site herbicide resistance, and propose that other mutations which increase ROS levels or decrease thaxtomin A metabolism could confer thaxtomin A resistance in the field. AUTHOR SUMMARY Modern agriculture relies on herbicides to control weed populations. However, herbicide resistance in weeds threatens the efficacy of herbicides and global crop production, similar to how antibiotic resistance poses a global health threat. Understanding the molecular mechanisms behind herbicide resistance helps to prevent resistance from evolving and to better manage herbicide resistant weeds in the field. Here, we use a forward genetic approach in the model species Marchantia polymorpha to discover novel mechanisms of herbicide resistance. We report the discovery of a novel mechanism of herbicide resistance caused by loss-of-function mutations in the Mp RTN4IP1L gene. We find that Mp rtn4ip1l mutants are resistant to the herbicides thaxtomin A and isoxaben, accumulate higher levels of reactive oxygen species than wild type plants, and are defective in thaxtomin A metabolism. We predict that loss-of-function mutations or treatments that increase reactive oxygen species production could contribute to thaxtomin A tolerance.
Article
Full-text available
Doxorubicin (DOX) is used as an anticancer drug despite its several side effects, especially its irreversible impacts on cardiotoxicity. Coenzyme Q10 (Q10) as a powerful antioxidant and lisinopril (LIS) as an angiotensin-converting enzyme inhibitor seem to provide protection against DOX-induced cardiotoxicity. Therefore, this study aimed to assess the cardioprotective effects of Q10 and LIS against DOX-induced cardiotoxicity in rats. Adult male Sprague–Dawley rats were randomly assigned into the control, LIS, Q10, DOX, DOX + LIS, and DOX + Q10 groups. On day 21, ECG was recorded and the right ventricle was dissected for evaluation of catalase activity and malondialdehyde (MDA) concentration. Additionally, the left ventricle and the sinoatrial (SA) node were dissected to assess the stereological parameters. The results of ECG indicated bradycardia and increase in QRS duration and QT interval in the DOX group compared to the control group. Meanwhile, the total volumes of the left ventricle, myocytes, and microvessels and the number of cardiomyocyte nuclei decreased, whereas the total volume of the connective tissue and the mean volume of cardiomyocytes increased in the DOX group. On the other hand, the SA node and the connective tissue were enlarged, while the volume of the SA node nuclei was reduced in the DOX group. Besides, catalase activity was lower and MDA concentration was higher in the DOX‐treated group. Q10 could recover most stereological parameters, catalase activity, and MDA concentration. LIS also prevented some stereological parameters and ECG changes and improved catalase activity and MDA concentration in the DOX group. The findings suggested that Q10 and LIS exerted cardioprotective effects against DOX-induced cardiac toxicity.
Chapter
Coenzyme Q (CoQ) is a lipidic molecule that transfers electrons between complexes I and II to complex III in the mitochondrial respiratory chain. It is also essential for processes mediated by other mitochondrial dehydrogenases, such as those involved in pyrimidine nucleotides biosynthesis, beta-oxidation and sulfide biosynthesis. A nuclear-encoded multiprotein complex at the inner mitochondrial membrane drives CoQ biosynthesis, which requires at least 13 proteins, leastways in yeasts. Mutations in the genes (COQ genes) coding for these proteins cause a decrease of CoQ biosynthesis rate leading to primary CoQ deficiency, a very heterogeneous group of mitochondrial diseases affecting different tissues and organs, and showing variable severity and age of onset. In general, this primary condition shows a good response to the supplementation with high doses of CoQ, but early diagnosis is compulsory to limit tissue damage. However, sometimes effectiveness is reduced, possibly due to its low bioavailability and, probably, difficulties crossing the blood-brain barrier. Secondary CoQ deficiency is a more common condition, in which defects of diverse mitochondrial processes induce an adaptive CoQ decrease. Secondary deficiency can be caused by oxidative phosphorylation (OXPHOS) defects, such as complex III dysfunction or mitochondrial DNA (mtDNA) depletion, or even non-OXPHOS mitochondrial defects. Here, we review the current knowledge of CoQ biosynthesis pathway, the genetic defects leading to primary deficiency and those conditions in which mitochondrial defects cause secondary deficiency.
Chapter
Plants do not have an essential demand for selenium (Se) to support their metabolism; however, they can take up Se in either inorganic or organic forms. Selenate is the major form of Se absorbed by plants in most soils. Because of its chemical similarity with sulfate, it is taken up and translocated throughout the plant via sulfate transporters. Selenite, conversely, prevails in anoxic soils and spans the cell membranes via aquaporins, phosphate, and silicon transporters. Once in the plant, Se is assimilated along the sulfur (S) assimilation pathway and converted into Se-amino acids that may benefit food crop consumers. Thus, the increase in the plant’s ability to take up and tolerate Se is relevant in the context of biofortification. Furthermore, Se-fortified plants can be employed for the remediation of Se-polluted soils. So far, conventional breeding is the most used method of enriching plants in Se. Alternatively, genetic engineering can be exploited to develop transgenics with substantial capacity to absorb and accumulate Se in the aboveground parts, particularly benefiting from the genetic pool of Se hyperaccumulators. Most of the transgenics assayed in the field overexpress Se/S assimilation enzymes, but other novel targets of genetic manipulation determining an increase of Se accumulation and tolerance have been identified. In light of this, this chapter aims at dissecting established and promising targets of genetic engineering responsible for enhanced Se tolerance and accumulation in non-hyperaccumulator plants.KeywordsSeleniumToleranceSe enrichmentHyperaccumulatorsGenetic engineering
Article
Zusammenfassung Coenzym Q10 ist ein ubiquitäres endogenes Chinon-Derivat, das in den biologischen Membranen der Körperzellen und als antioxidative Komponente in zirkulierenden Lipoproteinen vorkommt. Das Vitaminoid spielt eine wichtige Rolle bei der Energieproduktion in den Mitochondrien. Eine unzureichende Versorgung mit Coenzym Q10, wie sie bei Erkrankungen mit oxidativem Stress häufig vorkommt, ist mit einer allgemeinen Abnahme der psychischen und physischen Leistungsfähigkeit verbunden. Coenzym Q10 und seine reduzierte Form Ubiquinol haben sich mittlerweile in der Prävention und Therapie einer Vielzahl von Erkrankungen klinisch bewährt.
Book
Full-text available
PRINT/ONLINE PRICING OPTIONS AVAILABLE UPON REQUEST AT [email protected] © 2005 by Marcel Dekker (except as noted on the opening page of each article). All Rights Reserved.
Article
Full-text available
We investigated the effect of in vitro and in vivo CoQ 10 supplementation on the recovery of lymphocytes from oxidative DNA damage. Furthermore, we investigated whether CoQ 10 supplementation modulates the activity of DNA repair enzymes by using cellular extracts from lymphocytes. Exposure of lymphocytes to oxidizing agents leads to an increase of DNA strand breaks, oxidized purines, and pyrimidines. Enrichment of cells with CoQ 10 prevents DNA strand-break formation and affects the kinetics of repair, which occurs faster in enriched than in native lymphocytes. In contrast, CoQ 10 supplementation neither prevents endogenous formation of oxidized bases nor affects their repair. DNA repair enzyme activity is enhanced by in vivo CoQ 10 supplementation. Changes in the redox state of several transcriptional factors have been proposed as mechanisms regulating cell proliferation and apoptosis. Because CoQ 10 is mainly present as ubiquinol-10, both in plasma and lymphocytes, it can feasibly modulate the intracellular redox potential involved in the regulation of gene expression. The redox mechanism implicated in the enzyme transactivation could explain the property of CoQ 10 to enhance the DNA repair activity and protect DNA from oxidative damage.
Article
Full-text available
Caloric restriction (CR) is known as the only non-genetic method proven to slow the rate of aging and extend lifespan in animals. Free radicals production emerges from normal metabolic activity and generates the accumulation of oxidized macromolecules, one of the main characteristics of aging. Due to its central role in cell bioenergetics, a great interest has been paid to CR-induced modifications in mitochondria, where CR has been suggested to decrease reactive oxygen species production. The plasma membrane contains a trans-membrane redox system (PMRS) that provides electrons to recycle lipophilic antioxidants, such as α-tocopherol and coenzyme Q (CoQ), and to modulate cytosolic redox homeostasis. In the present study, we have investigated age differences in the PMRS in mouse liver and their modulation by CR. Aging induced a decrease in the ratio of CoQ10/CoQ9 and α-tocopherol in liver PM from AL-fed mice that was attenuated by CR. CoQ-dependent NAD(P)H dehydrogenases highly increased in CR old mice liver PMs. On the other hand, the CoQ-independent NADH-FCN reductase activity increased in AL-fed animals; whereas, in mice under CR this activity did not change during aging. Our results suggest that liver PMRS activity changes during aging and that CR modulates these changes. By this mechanism CR maintains a higher antioxidant capacity in liver PM of old animals by increasing the activity of CoQ-dependent reductases. Also, the putative role of PMRS in the modulation of redox homeostasis of cytosol is implicated.
Article
Full-text available
Coenzyme Q (Q) is reduced in plasma membrane and mitochondria by NAD(P)H-dependent reductases providing reducing equivalents to maintain both respiratory chain and antioxidant protection. Reactive oxygen species (ROS) are accumulated in the aging process originating mainly in mitochondria but also in other membranes, such as plasma membrane partially by the loss of electrons from the semiquinone. The reduction of Q by NAD(P)H-dependent reductases in plasma membrane is responsible for providing its antioxidant capacity, preventing both the lipid peroxidation chain and the activation of the ceramide-dependent apoptosis pathway. Both Q content and its reductases are decreased in plasma membrane of aging mammals. Calorie restriction, which extends mammal life span, increases the content of Q in the plasma membrane and also activates Q reductases in this membrane. Both lipid peroxidation and ceramide production are decreased in the plasma membrane in calorie-restricted animals. Plasma membrane is, then, an important cellular component to control the aging process through its concentration and redox state of Q.
Article
Full-text available
Redox chemistry-the transfer of electrons or hydrogen atoms--is central to energy conversion in respiration and photosynthesis. In photosynthesis in chloroplasts, two separate, light-driven reactions, termed photosystem I and photosystem II, are connected in series by a chain of electron carriers. The redox state of one connecting electron carrier, plastoquinone, governs the distribution of absorbed light energy between photosystems I and II by controlling the phosphorylation of a mobile, light-harvesting, pigment- protein complex. Here we show that the redox state of plastoquinone also controls the rate of transcription of genes encoding reaction-centre apoproteins of photosystem I and photosystem II. As a result of this control, the stoichiometry between the two photosystems changes in a way that counteracts the inefficiency produced when either photosystem limits the rate of the other. In eukaryotes, these reaction-centre proteins are encoded universally within the chloroplast. Photosynthetic control of chloroplast gene expression indicates an evolutionary explanation for this rule: the redox signal-transduction pathway can be short, the response rapid, and the control direct.
Article
Full-text available
With the recognition of the central role of mitochondria in apoptosis, there is a need to develop specific tools to manipulate mitochondrial function within cells. Here we report on the development of a novel antioxidant that selectively blocks mitochondrial oxidative damage, enabling the roles of mitochondrial oxidative stress in different types of cell death to be inferred. This antioxidant, named mitoQ, is a ubiquinone derivative targeted to mitochondria by covalent attachment to a lipophilic triphenylphosphonium cation through an aliphatic carbon chain. Due to the large mitochondrial membrane potential, the cation was accumulated within mitochondria inside cells, where the ubiquinone moiety inserted into the lipid bilayer and was reduced by the respiratory chain. The ubiquinol derivative thus formed was an effective antioxidant that prevented lipid peroxidation and protected mitochondria from oxidative damage. After detoxifying a reactive oxygen species, the ubiquinol moiety was regenerated by the respiratory chain enabling its antioxidant activity to be recycled. In cell culture studies, the mitochondrially localized antioxidant protected mammalian cells from hydrogen peroxide-induced apoptosis but not from apoptosis induced by staurosporine or tumor necrosis factor-α. This was compared with untargeted ubiquinone analogs, which were ineffective in preventing apoptosis. These results suggest that mitochondrial oxidative stress may be a critical step in apoptosis induced by hydrogen peroxide but not for apoptosis induced by staurosporine or tumor necrosis factor-α. We have shown that selectively manipulating mitochondrial antioxidant status with targeted and recyclable antioxidants is a feasible approach to investigate the role of mitochondrial oxidative damage in apoptotic cell death. This approach will have further applications in investigating mitochondrial dysfunction in a range of experimental models.
Article
Full-text available
We wish to elaborate a novel mechanism of metabolic regulation mediated by cytoplasmic tyrosine phosphatases and kinases. Briefly we propose that phosphofructokinase, aldolase, and glyceraldehyde-3-phosphate dehydrogenase (G3PDH) bind reversibly to the N-terminus of the cytoplasmic domain of band 3. Once the enzymes are bound, they are inhibited; however, upon release they are restored to full activity. We demonstrate that control of enzyme binding and consequently control of substrate flow down the pathway is executed by phosphorylation of Tyr 8 and Tyr 21 within the glycolytic enzyme binding site at the N-terminus of band 3. This phosphorylation results in obstruction of enzyme binding, leading to enzyme activation. Importantly, the tyrosine kinase that phosphorylates band 3 is activated by oxidation, while the tyrosine phosphatase that dephosphorylates band 3 is inhibited by the same redox changes. Consequently, treatment of red cells wih oxidants such as H2O2 and ferricyanide can enhance both tyrosine phosphorylation of the N-terminus of band 3 and glycolysis in a coordinate manner. Because oxidant entry into the cell is not essential, a plasma membrane electron transport pathway is believed to mediate the oxidant's effects.
Article
Full-text available
Friedreich's ataxia (FRDA) is an autosomal recessive, degenerative disease that involves the central and peripheral nervous systems and the heart. A gene, X25, was identified in the critical region for the FRDA locus on chromosome 9q13. The gene encodes a 210-amino acid protein, frataxin, that has homologs in distant species such as Caenorhabditis elegans and yeast. A few FRDA patients were found to have point mutations in X25, but the majority were homozygous for an unstable GAA trinucleotide expansion in the first X25 intron.
Chapter
Coenzyme Q is a lipid with broad distribution in nature, present in plants, bacteria, fungi, and all animal tissues. Coenzyme Q refers to a general structure composed of a nucleus, i.e., 2,3-dimethoxy-5-methylbenzoquinone, and, substituted at position 6 of this quinone, a side chain consisting of isoprene units (5 carbons), all in trans configuration and with one double bond. In human tissues, the major part of coenzyme Q is coenzyme Q10, which has 10 isoprenoid units; only 2-7% is present as coenzyme Q9.
Article
Background Recommendations for monitoring levels of transaminases (alanine aminotransferase and aspartate aminotransferase) and of creatine kinase (CK) in patients taking 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) vary and are not based on data from clinical practice. We performed a study to determine the yield of routine screening of aminotransferase and CK levels among patients taking statins. Methods We performed a retrospective review of a primary care practice's computerized medical record. A computerized search identified all patients with a statin on their medication list and gave their alanine aminotransferase, aspartate aminotransferase, and CK values for 1998. We reviewed the records of all patients for whom these values were significantly or moderately abnormal to determine the values' relationship to statin therapy and outcomes. Results During the year of the study, 1014 (85%) of the 1194 patients who had a statin on their medication list had at least 1 monitoring test performed. Of these 1014 patients, 10 (1.0%) had a significant elevation and 5 (0.5%) a moderate elevation of transaminase levels, but none of these abnormalities appeared to be related to statin use. Moreover, 6 (0.9%) patients had at least 1 significantly abnormal CK value but it did not appear to be attributable to a statin; and of the 14 (2.1%) patients who had a moderate CK elevation, it was potentially due to a statin in only 2. There were no documented adverse sequelae associated with these abnormal results. Conclusions In this study of statin use in a primary care practice, routine monitoring revealed no cases of significantly or moderately abnormal transaminase values attributable to statins. No significantly abnormal and only 2 moderately abnormal CK values were potentially attributable to statin use. This study questions the usefulness of routine measurement of transaminase and CK levels in all patients taking statins.
Article
To determine whether chronic treatment with coenzyme Q10 or remacemide hydrochloride slows the functional decline of early Huntington's disease (HD). METHODS: The authors conducted a multicenter, parallel group, double-blind, 2 x 2 factorial, randomized clinical trial. Research participants with early HD (n = 347) were randomized to receive coenzyme Q10 300 mg twice daily, remacemide hydrochloride 200 mg three times daily, both, or neither treatment, and were evaluated every 4 to 5 months for a total of 30 months on assigned treatment. The prespecified primary measure of efficacy was the change in total functional capacity (TFC) between baseline and 30 months. Safety measures included the frequency of clinical adverse events. RESULTS: Neither intervention significantly altered the decline in TFC. Patients treated with coenzyme Q10 showed a trend toward slowing in TFC decline (13%) over 30 months (2.40- versus 2.74-point decline, p = 0.15), as well as beneficial trends in some secondary measures. There was increased frequency of nausea, vomiting, and dizziness with remacemide and increased frequency of stomach upset with coenzyme Q10. CONCLUSIONS: Neither remacemide nor coenzyme Q10, at the dosages studied, produced significant slowing in functional decline in early HD.
Article
: The oxidative modification of proteins by reactive species, especially reactive oxygen species, is implicated in the etiology or progression of a panoply of disorders and diseases. These reactive species form through a large number of physiological and non-physiological reactions. An increase in the rate of their production or a decrease in their rate of scavenging will increase the oxidative modification of cellular molecules, including proteins. For the most part, oxidatively modified proteins are not repaired and must be removed by proteolytic degradation, and a decrease in the efficiency of proteolysis will cause an increase in the cellular content of oxidatively modified proteins. The level of these modified molecules can be quantitated by measurement of the protein carbonyl content, which has been shown to increase in a variety of diseases and processes, most notably during aging. Accumulation of modified proteins disrupts cellular function either by loss of catalytic and structural integrity or by interruption of regulatory pathways.
Article
Evidence is presented that the transport of lipid-soluble ions through bilayer membranes occurs in three distinct steps: (1) adsorption to the membranesolution interface; (2) passage over an activation barrier to the opposite interface; and (3) desorption into the aqueous solution. Support for this mechanism comes from a consideration of the potential energy of the ion, which has a minimum in the interface. The formal analysis of the model shows that the rate constants of the individual transport steps can be determined from the relaxation of the electric current after a sudden change in the voltage. Such relaxation experiments have been carried out with dipicrylamine and tetraphenylborate as permeable ions. In both cases the rate-determining step is the jump from the adsorption site into the aqueous phase. Furthermore, it has been found that with increasing ion concentration the membrane conductance goes through a maximum. In accordance with the model recently developed by L. J. Bruner, this behavior is explained by a saturation of the interface, which leads to a blocking of the conductance at high concentrations.
Article
In this report, we describe the electron paramagnetic resonance (EPR) spectroscopic characterizations of the fast-relaxing ubisemiquinone (SQ(Nf)) species associated with NADH-ubiquinone oxidoreductase (complex I) detected in tightly coupled submitochondrial particles (SMP). The signals of SQ(Nf) are observed only in the presence of delta muH+, whereas other slowly relaxing SQ species, SQ(Ns) and SQ(Nx), are not sensitive to delta muH+. In this study, we resolved the EPR spectrum of the delta muH+-sensitive SQ(Nf), which was trapped during the steady-state NADH-Q1 oxidoreductase reaction, as the difference between coupled and uncoupled SMP. Thorough analyses of the temperature profile of the resolved SQ(Nf) signals have revealed previously unrecognized spectra from delta muH+-sensitive SQ(Nf) species. This newly detected SQ(Nf) signals are observable only below 25 K, similar to the cluster N2 signals, and exhibit a doublet signal with a peak-to-peak separation (deltaB) of 56 G. In this work, we identify the partner to the interacting cluster N2. We have analyzed the g = 2.00 and g = 2.05 splittings using a computer simulation program that includes both exchange and dipolar interactions as well as the g-strain effect. Computer simulation of these interaction spectra showed that cluster N2 and fast-relaxing SQ(Nf) species undergo a spin-spin interaction, which contains both exchange (55 MHz) and dipolar interaction (16 MHz) with an estimated center-to-center distance of 12 A. This finding delineates an important functional role for this coupled [(N2)(red)-SQ(Nf)] structure in complex I, which is discussed in connection with electron transfer and energy coupling.
Article
The appearance of a voltametric technique for measuring the redox poise of the ubiquinone pool during the course of electron transfer (Moore et al. (1988) FEBS Lett. 235: 76–80) has facilitated attempts to understand the regulation of electron flow between the main and the cyanide-resistant (alternative) electron transfer chains in isolated plant mitochondria. In the present study, a two-step reduction model describing electron flow between the ubiquinone pool and the alternative oxidase is developed based upon ‘Q-pool’ assumptions. The steady-state rate equation that results from this model is used to simulate data describing the relationship between Q-pool redox poise and alternative pathway activity in mitochondria isolated from several plant sources. These simulations provide a better fit to the observed relationship than those associated with previous models. The simulations also indicate that variations in the observed relation between Q-pool reduction state and alternative pathway activity among different plant mitochondria is mainly associated with differences in the rates of reaction between the reduced oxidase and oxidized ubiquinone, and further suggest that the reduction of oxygen by the alternative oxidase proceeds via the initial formation of a four-electron reduced enzyme. The derived kinetic rate equation for the two-step reduction model also explains the source of the low apparent Km for oxygen of the alternative oxidase and provides some insights into conditions under which the alternative pathway velocity should display a greater dependence upon oxygen concentration.
Article
The objective of this study was to compare the relative bioavailability of two new products with solubilized and non-solubilized over-the-counter (OTC) coenzyme Q10 products. Nine healthy adults were given single 180 mg doses of each coenzyme Q10 formulation at two week intervals. A commercially-marketed, non-solubilized Q10 powder formulation (product D) was only minimally absorbed, and was excluded from the analysis of data. ANOVA comparison of maximum plasma concentrations (Cmax), time of maximum concentrations (tmax), areas under the concentration-time curves from times zero to 144 hours post dose (AUC0-144h), and areas under the concentration-time curves from times zero to infinity (AUC0-∞) were not significantly different (P > 0.05) between test products A (LiQ-10™) and B (Q-Nol™) and the reference product C (UbiQGel®). The upper limits of the 90% confidence intervals of the log-transformed ratios (A:C and B:C) of Cmax, AUC0-144h, and AUC0-∞ were >1.25 for both test products, but significant (P < 0.05) only for the B:C AUC0-144h. The results of this study indicate that LiQ-10™ has increased bioequivalence compared to the reference product, but did not reach statistical significance. Q-Nol™ has increased bioavailability compared to the reference product (P < 0.05).
Article
A randomized cross-over study by supplementation with single doses of coenzyme Q10 (30 mg/person), administered either as a meal consisting of cooked pork heart or as 30 mg coenzyme Q10 capsules was performed to investigate the bioavailability of dietary coenzyme Q10 in humans. The increase in serum coenzyme Q10 concentration was used as an index of the absorption, and reached a maximum six hours after the ingestion of either meal or capsules. Following intake of coenzyme Q10 capsules, the serum coenzyme Q10 concentrations increased significantly (p
Article
The proton-pumping NADH:ubiquinone oxidoreductase, also called complex I, is the first of the respiratory complexes providing the proton motive force which is essential for energy consuming processes like the synthesis of ATP. Homologues of this complex exist in bacteria, archaea, in mitochondria of eukaryotes and in chloroplasts of plants. The bacterial and mitochondrial complexes function as NADH dehydrogenase, while the archaeal complex works as F420H2 dehydrogenase. The electron donor of the cyanobacterial and plastidal complex is not yet known. Despite the different electron input sites, 11 polypeptides constitute the structural framework for proton translocation and quinone binding in the complex of all three domains of life. Six of them are also present in a family of membrane-bound multisubunit [NiFe] hydrogenases. It is discussed that they build a module for electron transfer coupled to proton translocation.
Article
We measured the lateral diffusion of different coenzyme Q homologues and analogues in model lipid vesicles using the fluorescence collisional quenching technique with pyrene derivatives and found diffusion coefficients in the range of 10−6 cm2/s. Theoretical diffusion coefficients for these highly hydrophobic components were calculated according to the free volume theory. An important parameter in the free volume theory is the relative dimension between diffusant and solvent: a molecular dynamics computer simulation of the coenzymes yielded their most probable geometries and volumes and revealed surprisingly similar sizes of the short and long homologues, due to a folded structure of the isoprenoid chain in the latter, with a length for coenzyme Q10 of 21 Å. Using this information we were able to calculate diffusion coefficients in the range of 10−6 cm2/s, in good agreement with those found experimentally.
Article
The vitamin-like nutrient CoQ10 (ubiquinone), discovered in 1957 and first used in human illness in 1967, has a crucial role in cellular ATP production as the coenzyme for mitochondrial complexes I, II and III. CoQ10 is also a lipid soluble antioxidant with cell protective effects. The past 30 years of clinical study have focused on congestive heart failure, ischaemic heart disease, angina, and myocardial protection during open-heart surgery. Measurably low blood and tissue levels of CoQ10 are evident in heart failure and may be normalised with oral CoQ10 supplementation, which has in turn been associated with measurable clinical improvement. Benefits observed in angina as well as objective measurement of ischaemia are believed to be related to both the bioenergetic and antioxidant properties of CoQ10 Recent studies of CoQ10 supplementation during open heart surgery showing an improvement in postoperative recovery have suggested a myocardial protective effect. The growing appreciation of the clinical relevance of CoQ10 depletion has caused concern over the CoQ10-lowering effect of the increasingly more potent and popular HMG-CoA reductase inhibitors (statins). Overall, CoQ10 appears to be a unique addition to standard medical therapy for cardiovascular disease.
Article
The localization of ubiquinone has been investigated in phospholipid bilayer vesicles in studies of fluorescence quenching of membrane-bound probes by ubiquinone homologs (Qn, where n is the number of the isoprenoid units of the chain). Fluorescence-quenching data obtained by using a set of anthroylstearate probes, having the fluorophore located at different depths, revealed that ubiquinone-3 is located throughout the whole bilayer thickness. From the bimolecular quenching constants in the membrane, lateral diffusion coefficients in two dimensions were calculated to span values of 10−7–10−6 cm2∙s−1. This suggests that ubiquinones laterally diffuse in a very fluid environment. On this basis, it is proposed that their translational diffusion in the bilayer takes place in two dimensions, with the quinone ring oscillating between the two bilayer surfaces within a hydrophobic environment not extending beyond the glycerol region. This model implies that the quinonic head is both settled near the polar surface of the bilayer and buried into the host hydrocarbon interior. This two-site distribution was confirmed for all Qn, except Q0, by their linear dichroism spectra in the bilayers provided by disc-like lyotropic nematic liquid crystals. These spectra also provided detailed information on the preferential orientations of the quinonic head of the different derivatives within the two sites. The mechanism by which the localization and orientation of Qn guest molecules inside the host bilayer is modulated by the isoprenoid chain length is discussed on a thermodynamical basis. Being that Qn is expected to be also widely contained in the highly curved cristae of the mitochondrial inner membrane, by using rod-like lyotropic nematic liquid crystals we searched out effects of the curvature of the host bilayer on those Qn distributions. The linear dichroism measurements reveal that Qn guest molecules are no longer obliged to find a partition between two different types of localizations when the host bilayer is highly curved. In this case all Qn, even the longest Q10, were found to stay parallel to the amphiphilic chains with a single site localization of the head near the polar interface. By the same linear dichroism technique, the local ordering of all Qn derivatives was also evaluated. The order parameters were found to be basically the same for all derivatives. This result is justified on the basis of the relaxation, caused by the surface curvature, of the lateral compression of the host chains.Key words: coenzyme Q (ubiquinone), fluorescence quenching, lateral diffusion, linear dichroism, model bilayers.
Article
We consider possible contributions of plasma membrane redox systems to Aging control by sirtuin (SIR). Reported changes in plasma membrane redox introduced by calorie restriction (CR) may lead to activation of SIR. The most obvious effect would lie in the increase of NAD+ as a result of NADH oxidation. So the question arises, do the observed changes herald an increase in NADH oxidase under CR? The other possibility is an increase in expression of SIR by activation of plasma membrane oxidase. Previous experiments have shown that activation of the plasma membrane redox system can increase cellular NAD+ concentration. The plasma membrane redox systems are also involved in control of protein kinase activity through oxygen radical generation. This activity may be related to control of SIR expression.
Article
Mutations in the Caenorhabditis elegans gene clk-1 affect biological timing and extend longevity. The gene clk-1 was identified, and the cloned gene complemented the clk-1 phenotypes and restored normal longevity. The CLK-1 protein was found to be conserved among eukaryotes, including humans, and structurally similar to the yeast metabolic regulator Cat5p (also called Coq7p). These proteins contain a tandem duplication of a core 82-residue domain. clk-1 complemented the phenotype of cat5/coq7 null mutants, demonstrating that clk-1 and CAT5/COQ7 share biochemical function and that clk-1 acts at the level of cellular physiology.
Article
The mitochondrial oxidative phosphorylation (OXPHOS) system is the final biochemical pathway in the production of ATP. The OXPHOS system consists of five multiprotein complexes, the individual subunits of which are encoded either by the mitochondrial or by the nuclear genome. Defects in the OXPHOS system result in devastating, mainly multisystem, diseases, and recent years have seen the description of the underlying genetic mutations in mitochondrial and nuclear genes. Advances in this arena have profited from progress in various genome projects, as well as improvements in our ability to create relevant animal models.
Article
Friedreich ataxia (FRDA), the most common autosomal recessive neurodegenerative disease among Europeans and people of European descent, is characterized by an early onset (usually before the age of 25), progressive ataxia, sensory loss, absence of tendon reflexes and pyramidal weakness of the legs1, 2, 3, 4. We have recently identified a unique group of patients whose clinical presentations are characterized by autosomal recessive inheritance, early age of onset, FRDA-like clinical presentations and hypoalbuminemia. Linkage to the FRDA locus, however, was excluded. Given the similarities of the clinical presentations to those of the recently described ataxia with oculomotor apraxia (AOA) linked to chromosome 9p13, we confirmed that the disorder of our patients is also linked to the same locus5. We narrowed the candidate region and have identified a new gene encoding a member of the histidine triad (HIT) superfamily as the 'causative' gene. We have called its product aprataxin; the gene symbol is APTX. Although many HIT proteins have been identified, aprataxin is the first to be linked to a distinct phenotype.