Placido Navas

Placido Navas
Universidad Pablo de Olavide | UPO · Centro Andaluz de Biología del Desarrollo

PhD

About

374
Publications
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19,312
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Publications

Publications (374)
Article
Full-text available
ADCK2 haploinsufficiency-mediated mitochondrial coenzyme Q deficiency in skeletal muscle causes mitochondrial myopathy associated with defects in beta-oxidation of fatty acids, aged-matched metabolic reprogramming, and defective physical performance. Calorie restriction has proven to increase lifespan and delay the onset of chronic diseases associa...
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 enviro...
Article
Full-text available
Primary coenzyme Q10 (CoQ) deficiency includes a heterogeneous group of mitochondrial diseases characterized by low mitochondrial levels of CoQ due to decreased endogenous biosynthesis rate. These diseases respond to CoQ treatment mainly at the early stages of the disease. The advances in the next generation sequencing (NGS) as whole-exome sequenci...
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...
Article
Coenzyme Q10 (CoQ10 ) deficiency is a rare disease characterized by a decreased accumulation of CoQ10 in cell membranes. Considering that CoQ10 synthesis and most of its functions are carried out in mitochondria, CoQ10 deficiency cases are usually considered a mitochondrial disease. A relevant feature of CoQ10 deficiency is that it is the only mito...
Article
Full-text available
Chronic nutrient excess leads to metabolic disorders and insulin resistance. Activation of stress-responsive pathways via Nrf2 activation contributes to energy metabolism regulation. Here, inducible activation of Nrf2 in mice and transgenesis of the Nrf2 target, NQO1, conferred protection from diet-induced metabolic defects through preservation of...
Article
SARS-CoV-2 causes a severe pneumonia (COVID-19) that affects essentially elderly people. In COVID-19, macrophage infiltration into the lung causes a rapid and intense cytokine storm leading finally to a multi-organ failure and death. Comorbidities such as metabolic syndrome, obesity, type 2 diabetes, lung and cardiovascular diseases, all of them ag...
Article
Full-text available
Coenzyme Q10 (CoQ) treatment monitoring is a matter of debate since CoQ distribution from plasma to blood cells and tissues is not fully understood. We aimed to analyze the CoQ levels in a wide set of human biological samples (plasma, blood mononuclear cells (BMCs), platelets, urinary cells, and skeletal muscle) from a group of 11 healthy male runn...
Article
All metazoans depend on the consumption of O2 by the mitochondrial oxidative phosphorylation system (OXPHOS) to produce energy. In addition, the OXPHOS uses O2 to produce reactive oxygen species that can drive cell adaptations1-4, a phenomenon that occurs in hypoxia4-8 and whose precise mechanism remains unknown. Ca2+ is the best known ion that act...
Article
Full-text available
Ubiquinol, the reduced form of Coenzyme Q 10 (CoQ 10 ), is a key factor in bioenergetics and antioxidant protection. During competition, professional soccer players suffer from considerable physical stress causing high risk of muscle damage. For athletes, supplementation with several antioxidants, including CoQ 10 , is widely recommended to avoid o...
Article
Full-text available
Resveratrol (RSV) is a bioactive natural molecule that induces antioxidant activity and increases protection against oxidative damage. RSV could be used to mitigate damages associated to metabolic diseases and aging. Particularly, RSV regulates different aspects of mitochondrial metabolism. However, no information is available about the effects of...
Chapter
Coenzyme Q10 (CoQ10) is an essential factor for aerobic bioenergetics and antioxidant protection in cell membranes and blood plasma lipoproteins. It is a component of the electron transport chain in mitochondria and the trans plasma membrane electron transport. Its deficiency in human causes CoQ10 deficiency syndrome, a heterogeneous group of mitoc...
Article
Coenzyme Q 10 (CoQ 10 ) deficiency syndrome is a rare disease included in the family of mitochondrial diseases, which is a heterogeneous group of genetic disorders characterized by defective energy production. CoQ 10 biosynthesis in humans requires at least 11 gene products acting in a multiprotein complex within mitochondria. The high-throughput s...
Preprint
Full-text available
Fatty acids and glucose are the main bioenergetic substrates in mammals that are alternatively used during the transition between fasting and feeding. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2, a member of the aarF domain...
Article
Full-text available
Coenzyme Q (CoQ), a redox-active lipid, is comprised of a quinone group and a polyisoprenoid tail. It is an electron carrier in the mitochondrial respiratory chain, a cofactor of other mitochondrial dehydrogenases, and an essential antioxidant. CoQ requires a large set of enzymes for its biosynthesis; mutations in genes encoding these proteins caus...
Article
Full-text available
Identifying diseases displaying chronic low plasma Coenzyme Q10 (CoQ) values may be important to prevent possible cardiovascular dysfunction. The aim of this study was to retrospectively evaluate plasma CoQ concentrations in a large cohort of pediatric and young adult patients. We evaluated plasma CoQ values in 597 individuals (age range 1 month to...
Chapter
Calorie restriction is the most effective intervention with prolongevity effects in many of the organisms. Calorie restriction can be considered as the reduction of the intake of energy without reaching malnutrition. The effect of calorie restriction is not only reserved to an extended longevity but also delays the onset and reduces the progression...
Article
The mitochondrial intramembrane rhomboid protease PARL has been implicated in diverse functions in vitro, but its physiological role in vivo remains unclear. Here we show that Parl ablation in mouse causes a necrotizing encephalomyelopathy similar to Leigh syndrome, a mitochondrial disease characterized by disrupted energy production. Mice with con...
Article
Full-text available
Mitochondria are key in the metabolism of aerobic organisms and in ageing progression and age-related diseases. Mitochondria are essential for obtaining ATP from glucose and fatty acids but also in many other essential functions in cells including aminoacids metabolism, pyridine synthesis, phospholipid modifications and calcium regulation. On the o...
Article
Coenzyme Q10 (CoQ10) is a redox molecule critical for the proper function of energy metabolism and antioxidant defenses. Despite its essential role in cellular metabolism, the regulation of CoQ10 biosynthesis in humans remains mostly unknown. Herein, we determined that PPTC7 is a regulatory protein of CoQ10 biosynthesis required for human cell surv...
Preprint
Full-text available
Reactive oxygen species (ROS) generated by mitochondria are a well-known example of mitochondria-derived signals that can drive cell adaptations or trigger cell damage. This is the case of the increase in ROS upon acute hypoxia. However, the precise mechanism by which acute hypoxia triggers mitochondrial ROS production is still unknown. Mitochondri...
Article
Loss of skeletal muscle mass and function is a hallmark of aging. This phenomenon has been related to a dysregulation of mitochondrial function and proteostasis. Calorie restriction (CR) has been demonstrated to delay aging and preserve function until late in life, particularly in muscle. Recently, we reported the type of dietary fat plays an impor...
Preprint
Full-text available
The mitochondrial intramembrane rhomboid protease Parl has been implicated in diverse functions in vitro, but its physiological role in vivo remains unclear. Here we show that Parl ablation in mouse causes a striking necrotizing encephalomyelopathy similar to Leigh syndrome, a mitochondrial disease characterized by disrupted energy production. Mice...
Article
Full-text available
Aging is a multifactorial process which affects all animals. Aging as a result of damage accumulation is the most accepted explanation but the proximal causes remain to be elucidated. There is also evidence indicating that aging has an important genetic component. Animal species age at different rates and specific signalling pathways, such as insul...
Article
Objectives: Bioavailability of supplements with coenzyme Q10 (CoQ10) in humans seems to depend on the excipients of formulations and on physiological characteristics of the individuals. The aim of this study was to determine which factors presented in CoQ10 supplements affect the different response to CoQ10 in humans. Methods: We tested seven di...
Article
Introduction: Coenzyme Q10 (CoQ) deficiency syndromes comprise a growing number of genetic disorders. While primary CoQ deficiency syndromes are rare diseases, secondary deficiencies have been related to both genetic and environmental conditions, which are the main causes of biochemical CoQ deficiency. The diagnosis is the essential first step for...
Article
Reactive oxygen species (ROS) generated by mitochondria in acute hypoxia are a well-known example of mitochondria-derived signals that can drive cell adaptations. However, the precise mechanism by which they are produced is still unknown. Mitochondrial Ca2⁺ movements have been considered direct effectors in cell signaling; but the role ascribed so...
Article
Full-text available
Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH‐dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo...
Article
Full-text available
Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and an antioxidant in plasma membranes and lipoproteins. It is endogenously produced in all cells by a highly regulated pathway that involves a mitochondrial multiprotein complex. Defects in either the structural and/or regulatory components of CoQ complex or i...
Article
Full-text available
Mutations in COQ8B cause steroid-resistant nephrotic syndrome with variable neurological involvement. In yeast, COQ8 encodes a protein required for coenzyme Q (CoQ) biosynthesis, whose precise role is not clear. Humans harbor two paralogue genes: COQ8A and COQ8B (previously termed ADCK3 and ADCK4). We have found that COQ8B is a mitochondrial matrix...
Article
Introduction: Coenzyme Q is an essential component in the activity of the mitochondrial electron transport chain. Its synthesis involves, at least, a complex of ten different proteins. In this study, an attempt is made to determine the evolution of the expression of the genes involved in coenzyme Q synthesis during mouse ageing. Material and meth...
Article
Full-text available
Coenzyme Q10 (CoQ10 ) plays a crucial role in mitochondria as an electron carrier within the mitochondrial respiratory chain (MRC), and is an essential antioxidant. Mutations in genes responsible for CoQ10 biosynthesis (COQ genes) cause primary CoQ10 deficiency, a rare and heterogeneous mitochondrial disorder with no clear genotype-phenotype associ...
Article
Full-text available
Coenzyme Q10 (CoQ10) deficiency syndrome includes clinically heterogeneous mitochondrial diseases that show a variety of severe and debilitating symptoms. A multiprotein complex encoded by nuclear genes carries out CoQ10 biosynthesis. Mutations in any of these genes are responsible for the primary CoQ10 deficiency, but there are also different cond...
Article
Full-text available
Coenzyme Q is an essential lipid with redox capacity that is present in all organisms. In yeast its biosynthesis depends on a multiprotein complex in which Coq7 protein has both catalytic and regulatory functions. Coq7 modulates CoQ6 levels through a phosphorylation cycle, where dephosphorylation of three amino acids (Ser/Thr) by the mitochondrial...
Article
Full-text available
Laboratory data interpretation for the assessment of complex biological systems remains a great challenge, as occurs in mitochondrial function research studies. The classical biochemical data interpretation of patients versus reference values may be insufficient, and in fact the current classifications of mitochondrial patients are still done on ba...
Article
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We report the generation, CRISPR/Cas9-edition and characterization of induced pluripotent stem cell (iPSC) lines from a patient with coenzyme Q10 deficiency harboring the heterozygous mutation c.483G>C in the COQ4 gene. iPSCs were generated using non-integrative Sendai Viruses containing the reprogramming factors OCT4, SOX2, KLF4 and C-MYC. The iPS...
Article
COQ2 (p-hydroxybenzoate polyprenyl transferase) encodes the enzyme required for the second step of the final reaction sequence of Coenzyme Q10 (CoQ) biosynthesis. Its mutations represent a frequent cause of primary CoQ deficiency and have been associated with the widest clinical spectrum, ranging from fatal neonatal multisystemic disease to late-on...
Article
Decrease in muscle mass and performance with ageing is one of the main factors of frailty in the elderly. Maintenance of muscle performance by involving in physical activities is essential to increase independence and quality of life among elderly. The use of natural compounds with ergogenic activity in old people would increase the effect of moder...
Article
Full-text available
Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved h...
Article
We evaluated the coenzyme Q₁₀ (CoQ) levels in patients who were diagnosed with mitochondrial oxidative phosphorylation (OXPHOS) and non-OXPHOS disorders (n = 72). Data from the 72 cases in this study revealed that 44.4% of patients showed low CoQ concentrations in either their skeletal muscle or skin fibroblasts. Our findings suggest that secondary...
Data
Fig. S3 Representative gels stained with Ponceau S used to normalize quantifications of the different antibody bands shown in this paper.
Data
Fig. S1 Cross‐section of a proximal convoluted tubule (PCT) from a six‐month old control animal.
Data
Fig. S4 Correlation analyses between different glomerular filtration structures (panels A, B and C) and glomerular structures versus mitochondrial mass in epithelial cells from proximal convoluted tubules (D, E and F). Panel A shows filtration slits (FS) versus glomerular basal membrane (GBM) thickness; panel B, podocyte foot processes (PFP) versus...
Data
Fig. S2 Representative images of cytoplasm portions of PCT epithelial cells from control (A) and 18‐months CR‐submitted animals with different dietary fats (B, CRL; C, CRS and D, CRF) showing a relatively large number of mitochondria (arrows). In C and D swollen mitochondria are clearly visible. The bars are equal to 2 µm (N = nucleus).
Article
Full-text available
Cytochrome b5 reductases (CYB5R) are required for the elongation and desaturation of fatty acids, cholesterol synthesis and mono-oxygenation of cytochrome P450 enzymes, all of which are associated with protection against metabolic disorders. However, the physiological role of CYB5R in the context of metabolism, healthspan and aging remains ill-defi...
Article
Full-text available
Increased production of reactive oxygen species (ROS) has long been considered a cause of aging. However, recent studies have implicated ROS as essential secondary messengers. Here we show that the site of ROS production significantly contributes to their apparent dual nature. We report that ROS increase with age as mitochondrial function deteriora...
Article
Coenzyme Q (CoQ) is a unique electron carrier in the mitochondrial respiratory chain, which is synthesized on-site by a nuclear encoded multiprotein complex. CoQ receives electrons from different redox pathways, mainly NADH and FADH2 from tricarboxylic acid pathway, dihydroorotate dehydrogenase, electron transfer flavoprotein dehydrogenase and glyc...