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Publications (61)
The mitochondrial Ca ²⁺ uniporter (MCU) plays crucial role in intramitochondrial Ca ²⁺ uptake, allowing Ca ²⁺ -dependent activation of oxidative metabolism. In recent decades, the role of MCU pore-forming proteins has been highlighted in cancer. However, the contribution of MCU-associated regulatory proteins mitochondrial calcium uptake 1 and 2 (MI...
Long noncoding RNAs (lncRNAs) are a subclass of noncoding RNAs composed of more than 200 nucleotides without the ability to encode functional proteins. Given their involvement in critical cellular processes such as gene expression regulation, transcription, and translation, lncRNAs play a significant role in organism homeostasis. Breast cancer (BC)...
The mitochondrial Ca ²⁺ uniporter (MCU) plays crucial role in intramitochondrial Ca ²⁺ uptake, allowing Ca ²⁺ -dependent activation of oxidative metabolism. In recent decades, the role of MCU pore-forming proteins has been highlighted in cancer. However, the contribution of MCU-associated regulatory proteins mitochondrial calcium uptake 1 and 2 (MI...
While clinical evidence remains limited, an extensive amount of research suggests a beneficial role of n-3 polyunsaturated fatty acid supplementation in cancer treatment. One potential benefit is an improvement of protein homeostasis, but how protein metabolism depends on proinflammatory cytokines in this context remains unclear. Here, using the na...
Background and aims
Recent evidences highlight a role of the mitochondria calcium homeostasis in the development of colorectal cancer (CRC). To overcome treatment resistance, we aimed to evaluate the role of the mitochondrial sodium-calcium–lithium exchanger (NCLX) and its targeting in CRC. We also identified curcumin as a new inhibitor of NCLX.
M...
Background:
Cancer cachexia is a multifactorial syndrome characterized by involuntary and pathological weight loss, mainly due to skeletal muscle wasting, resulting in a decrease in patients' quality of life, response to cancer treatments, and survival. Our objective was to investigate skeletal muscle alterations in cachectic cancer patients.
Met...
Colorectal cancer (CRC) is associated with high mortality worldwide and new targets are needed to overcome treatment resistance. Recent evidences highlight a role of the mitochondria calcium homeostasis in the development of CRC. In this context, we aimed to evaluate the role of the mitochondrial sodium-calcium-lithium exchanger (NCLX) and its targ...
Despite improvements in therapeutic strategies for treating breast cancers, tumor relapse and chemoresistance remain major issues in patient outcomes. Indeed, cancer cells display a metabolic plasticity allowing a quick adaptation to the tumoral microenvironment and to cellular stresses induced by chemotherapy. Recently, long non-coding RNA molecul...
Since its discovery, mitophagy has been viewed as a protective mechanism used by cancer cells to prevent the induction of mitochondrial apoptosis. Most cancer treatments directly or indirectly cause mitochondrial dysfunction in order to trigger signals for cell death. Elimination of these dysfunctional mitochondria by mitophagy could thus prevent t...
White adipose tissue interacts closely with breast cancers through the secretion of soluble factors such as cytokines, growth factors or fatty acids. However, the molecular mechanisms of these interactions and their roles in cancer progression remain poorly understood. In this study, we investigated the role of fatty acids in the cooperation betwee...
Environment surrounding tumours are now recognized to play an important role in tumour development and progression. Among the cells found in the tumour environment, adipocytes from adipose tissue establish a vicious cycle with cancer cells to promote cancer survival, proliferation, metastasis and treatment resistance. This cycle is particularly of...
Cardiolipins (CLs) are specific phospholipids of the mitochondria composing about 20% of the inner mitochondria membrane (IMM) phospholipid mass. Dysregulation of CL metabolism has been observed in several types of cancer. In most cases, the evidence for a role for CL in cancer is merely correlative, suggestive, ambiguous, and cancer-type dependent...
Research investigators have shown a growing interest in investigating alterations underlying skeletal muscle wasting inpatients with cancer. However, skeletal muscle dysfunctions associated with cancer cachexia have mainly been studied inpreclinical models. In the present review, we summarize the results of clinical studies in which skeletal muscle...
Background: Changes in skeletal muscle mass (SMM), total adipose tissue mass (TAT) or bone mineral density (BMD) have been described in patients with cancer undergoing various treatments; simultaneous variations of all 3 tissues has not been reported.
Methods: Data were prospectively collected in a clinical study (NCT00489697) including patients w...
The aim of this study was to identify HPTLC (High Performance Thin Layer Chromatography) conditions allowing the separation and quantification of mammalian cellular phospholipids (sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, and especially phosphatidic acid, cardiolipin and monolysocardioli...
Metabolic reprogramming in tumours is now recognized as a hallmark of cancer, participating both in tumour growth and cancer progression. Cancer cells develop global metabolic adaptations allowing them to survive in the low oxygen and nutrient tumour microenvironment. Among these metabolic adaptations, cancer cells use glycolysis but also mitochond...
Background:
Mitochondrial Trifunctional Protein deficiency (TFPD) is a severe genetic disease characterized by altered energy metabolism and accumulation of long-chain (LC) acylcarnitines in blood and tissues. This accumulation could impair the mitochondrial oxidative phosphorylation (OxPhos), contributing to the non-optimal outcome despite conven...
Background:
We hypothesized that, among the mechanisms of drug-resistance acquired by doxorubicin (DOX)-resistant breast cancer cells to maintain cell survival, ATP-dependent drug efflux pumps could be expressed in their mitochondrial membranes and this might limit the accumulation of DOX in this subcellular compartment in relation to mitochondria...
Cardiolipin (CL) is a unique mitochondrial phospholipid potentially affecting many aspects of mitochondrial function/processes, i.e. energy production through oxidative phosphorylation. Most data focusing on implication of CL content and mitochondrial bioenergetics were performed in yeast or in cellular models of Barth syndrome. Previous work repor...
The metabolic syndrome covers metabolic abnormalities including obesity and type 2 diabetes (T2D). T2D is characterized by insulin resistance resulting from both environmental and genetic factors. A genome-wide association study (GWAS) published in 2010 identified TP53INP1 as a new T2D susceptibility locus, but a pathological mechanism was not iden...
Cancer-induced cachexia describes the progressive skeletal muscle wasting associated with many cancers leading to shortened survival time in cancer patients. We previously reported that cardiolipin content and energy-wasting processes were both increased in liver mitochondria in a rat model of peritoneal carcinosis (PC)-induced cachexia. To increas...
Mitochondrial membranes are essential for the good functioning of the organelle. For instance, the inner mitochondrial membrane contains the oxidative phosphorylation system that permits ATP synthesis. Phospholipids environment and especially cardiolipin are crucial for the mitochondrial energy metabolism. Indeed, cardiolipin is known to provide es...
Background
Cancer cachexia is a complex syndrome related to a negative energy balance resulting in muscle wasting. Implication of muscle mitochondrial bioenergetics alterations during cancer cachexia was suggested. Therefore, the aim of this study was to explore the efficiency of oxidative phosphorylation in skeletal muscle mitochondria in a precli...
Cancer cachexia is a dynamic process characterized by a negative energy balance induced by anorexia and hypermetabolism. The mechanisms leading to hypermetabolism are not totally elucidated. This study examines the efficiency of oxidative phosphorylation and energy wasting in liver mitochondria isolated from rats with cancer cachexia induced by per...
Undernutrition is frequently seen in cancer and is considered as a bad prognostic factor. The mechanisms involved in this complex syndrome are not fully understood. Systemic inflammation plays an important role in the occurrence and/or development of cancer-associated undernutrition. Although it is essential to counteract cancer-associated undernut...
Undernutrition is frequently seen in cancer and is considered as a bad prognostic factor. The mechanisms involved in this complex syndrome are not fully understood. Systemic inflammation plays an important role in the occurrence and/or development of cancer-associated undernutrition. Although it is essential to counteract cancer-associated undernut...
The aim of this study was to evaluate the effects of a fish oil (FO) diet (rich in long chain, n-3, polyunsaturated fatty acid) on cancer cachexia symptoms in rats. To this end, peritoneal carcinosis (PC) was generated by an intraperitoneal injection of cancer cells in BDIX rats fed FO or standard (Std) diets. Food intake and body weight were recor...
The precise cause of insulin resistance and type 2 diabetes is unknown. However, there is it strong association between insulin resistance and lipid accumulation - and, in particular, lipotoxic fatty acid metabolites - in insulin-target tissues. Such accumulation is known to cause insulin resistance, particularly in skeletal muscle, by reducing ins...
To study the effect of mitochondrial permeability transition pore (PTP) opening on NAD(P)H localization, intact cells were
exposed to the Ca2+ ionophore A23187. PTP opening, mitochondrial membrane potential, mitochondrial volume, and NAD(P)H localization were assessed
by time-lapse laser confocal microscopy using the calcein-cobalt technique, tetra...
The main objective of the study was to evaluate the effects of small increments in thyroxine (T4) levels following levothyroxine (L-T4) administration on the body composition of women patients. The secondary objective was to assess the effect of the therapy on energy expenditure and muscular function.
The prospective, randomized study consisted of...
The composition of the mitochondrial inner membrane and uncoupling protein [such as adenine nucleotide translocator (ANT)] contents are the main factors involved in the energy-wasting proton leak. This leak is increased by glucocorticoid treatment under nonphosphorylating conditions. The aim of this study was to investigate mechanisms involved in g...
Variable durations of food restriction (FR; lasting weeks to years) and variable FR intensities are applied to animals in life span-prolonging studies. A reduction in mitochondrial proton leak is suggested as a putative mechanism linking such diet interventions and aging retardation. Early mechanisms of mitochondrial metabolic adaptation induced by...
It had been thought for a long time that thyroid hormones were the only ones to regulate energy production within mitochondria. Recent findings show that other hormones (steroids, leptin, insulin) regulate the efficiency of mitochondrial adenosine triphosphate production. Furthermore, a mismatch between oxygen consumption and energy intake may not...
Glucocorticoid treatments are associated with increased whole-body oxygen consumption. We hypothesised that an impairment of muscle energy metabolism can participate in this increased energy expenditure.
To investigate this possibility, we have studied muscle energetics of dexamethasone-treated rats (1.5 mg kg(-1) day(-1) for 6 days), in vivo by (3...
Weight loss is frequently observed in clinical practice. When weight loss is unwanted
(undernutrition, hypercatabolism), whole body oxygen consumption is often increased, which
is paradoxical in face of anorexia. Our results show that food restriction induces a decrease in
liver mitochondrial respiration and respiratory chain activity, which is pro...
The present investigation was undertaken in order to evaluate the contributions of ATP synthesis and proton leak reactions to the rate of active respiration of liver mitochondria, which is altered following dexamethasone treatment (1.5 mg/kg per day for 5 days). We applied top-down metabolic control analysis and its extension, elasticity analysis,...
Since fat, relative to other macronutrients, has low satiety and high energy density, it may have therapeutic application for supplementing energy intake. This study compared the effect of isoenergetic (1050 kJ) high fat or high carbohydrate oral supplements, given at breakfast, on the short-term appetite and energy intake in undernourished elderly...
To examine the effect of 50% food restriction over a period of 3 days on mitochondrial energy metabolism, liver mitochondria were isolated from ad libitum and food-restricted rats. Mitochondrial enzyme activities and oxygen consumption were assessed spectrophotometrically and polarographically. With regard to body weight loss (-5%), food restrictio...
To examine the effect of 50% food restriction over a period of 3 days on mitochondrial energy metabolism, liver mitochondria were isolated from ad libitum and food-restricted rats. Mitochondrial enzyme activities and oxygen consumption were assessed spectrophotometrically and polarographically. With regard to body weight loss (-5%), food restrictio...
There is paramount evidence to suggest the importance of cell volume changes for the regulation of cell function, including protein metabolism. Among many other effects, cell swelling inhibits proteolysis and stimulates protein synthesis. However, most of the data pertinent to this theory relate to in vitro experiments. This paper reviews the evide...
The present investigation was undertaken to evaluate whether mitochondrial energy metabolism is altered in a model of malnutrition induced by dexamethasone (DEX) treatment (1.5 mg/kg per d for 5 d). The gastrocnemius and liver mitochondria were isolated from DEX-treated, pair-fed (PF) and control (CON) rats. Body weight was reduced significantly mo...
Carotenoids are thought to diminish the incidence of certain degenerative diseases, but the mechanisms involved in their intestinal absorption are poorly understood. Our aim was to obtain basic data on the fate of carotenoids in the human stomach and duodenum. Ten healthy men were intragastrically fed three liquid test meals differing only in the v...
We investigated the role that mitochondrial proton leak may play in the glucocorticoid-induced hypermetabolic state. Sprague-Dawley rats were injected with dexamethasone over a period of 5 days. Liver mitochondria and gastrocnemius subsarcolemmal and intermyofibrillar mitochondria were isolated from dexamethasone-treated, pair-fed and control rats....
Although the stimulating effect of thyroid hormones on energy metabolism has been recognized for more than a century, the relation between thyroid function and weight control and obesity remains unclear. We review here the effects of thyroid hormones, hyperthyroidism, and hypothyroidism on body composition and the parameters of energy metabolism.
Une perte de poids est une situation fréquemment rencontrée en médecine. Paradoxalement
quand elle est involontaire (dénutrition, hypercatabolisme), la consommation d'oxygène du
corps entier est augmentée. Cependant, les mécanismes biochimiques restent discutés. Nos
résultats montrent que la restriction calorique s'accompagne d'une diminution de l'...