20 results on '"Rossignol Rodrigue"'
Search Results
2. Nuclear control of lung cancer cells migration, invasion and bioenergetics by eukaryotic translation initiation factor 3F
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Esteves, Pauline, Dard, Laetitia, Brillac, Aurélia, Hubert, Christophe, Sarlak, Saharnaz, Rousseau, Benoît, Dumon, Elodie, Izotte, Julien, Bonneu, Marc, Lacombe, Didier, Dupuy, Jean-William, Amoedo, Nivea, and Rossignol, Rodrigue
- Abstract
The basic understanding of the biological effects of eukaryotic translation initiation factors (EIFs) remains incomplete, notably for their roles independent of protein translation. Different EIFs exhibit nuclear localization and DNA-related functions have been proposed, but the understanding of EIFs novel functions beyond protein translation lacks of integrative analyses between the genomic and the proteomic levels. Here, the noncanonical function of EIF3F was studied in human lung adenocarcinoma by combining methods that revealed both the protein–protein and the protein–DNA interactions of this factor. We discovered that EIF3F promotes cell metastasis in vivo. The underpinning molecular mechanisms involved the regulation of a cluster of 34 metastasis-promoting genes including Snail2, as revealed by proteomics combined with immuno-affinity purification of EIF3F and ChIP-seq/Q-PCR analyses. The interaction between EIF3F and signal transducer and activator of transcription 3 (STAT3) controlled the EIF3F-mediated increase in Snail2 expression and cellular invasion, which were specifically abrogated using the STAT3 inhibitor Nifuroxazide or knockdown approaches. Furthermore, EIF3F overexpression reprogrammed energy metabolism through the activation of AMP-activated protein kinase and the stimulation of oxidative phosphorylation. Our findings demonstrate the role of EIF3F in the molecular control of cell migration, invasion, bioenergetics, and metastasis. The discovery of a role for EIF3F–STAT3 interaction in the genetic control of cell migration and metastasis in human lung adenocarcinoma could lead to the development of diagnosis and therapeutic strategies.
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- 2020
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3. Intégration des données histo-pathologiques, biochimiques et génomiques dans le diagnostic des mitochondrio-pathies
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Trimouille, Aurélien, Courtois, Sarah, Angelini, Chloé, Amoedo, Nivea Dias, Durand, Christelle, Courreges, Armelle, Coupry, Isabelle, Goizet, Cyril, Rossignol, Rodrigue, Lacombe, Didier, Laquerriere, Annie, Espil, Caroline, Bidet, Audrey, Berenguer, Sophie, and Martin-Négrier, Marie-Laure
- Abstract
Les mitochondriopathies sont des maladies cliniquement hétérogènes ayant pour cause des mutations de l’ADN mitochondrial (ADNmt), ou des gènes mitochondriaux de l’ADN nucléaire. Si les analyses par séquençage haut-débit (NGS) permettent d’obtenir l’intégralité du génome des patients atteints, l’interprétation de ces données reste très complexe, notamment pour les pathologies peu ou pas décrites. L’intégration des données histo-pathologiques, biochimiques ou d’analyses fonctionnelles est donc indispensable pour aboutir au diagnostic. Nous présentons ici 3 cas pour lesquelles cette analyse multi-disciplinaire a été nécessaire.
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- 2023
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4. Bioenergetic Changes Underline Plasticity of Murine Embryonic Stem Cells
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Vlaski‐Lafarge, Marija, Loncaric, Darija, Perez, Laura, Labat, Véronique, Debeissat, Christelle, Brunet de la Grange, Philippe, Rossignol, Rodrigue, Ivanovic, Zoran, and Bœuf, Hélène
- Abstract
Murine embryonic stem cells (mESCs) are endowed by a time‐dependent window of plasticity during their early commitment steps. Indeed, while mESCs deprived of leukemia inhibitory factor (LIF) for 24 hours revert to their naive pluripotent state after subsequent LIF readdition, cells deprived of LIF for 48 hours are no longer efficient in reverting, upon LIF addition, and undergo irreversible differentiation. We investigated undisclosed bioenergetic profiles of early mESC‐derived committed cells versus their undifferentiated states in order to reveal specific bioenergetic changes associated with mESC plasticity. Multiparametric bioenergetic analysis revealed that pluripotent (+LIF) and reversibly committed cells (−LIF24h) are energetically flexible, depending on both oxidative phosphorylation (OXPHOS) and glycolysis. They exhibit high mitochondrial respiration in the presence of the main energetic substrates and can also rely on glycolysis in the presence of OXPHOS inhibitor. Inhibition of the glycolysis or mitochondrial respiration does not change drastically the expression of pluripotency genes, which remain well expressed. In addition, cells treated with these inhibitors keep their capacity to differentiate efficiently upon embryoid bodies formation. Transition from metabolically active mESCs to irreversibly committed cells is associated with a clear change in mitochondrial network morphology, to an increase of adenosine triphosphate (ATP) produced from glycolysis and a decline of ATP turnover and of the mitochondrial activity without change in the mitochondrial mass. Our study pointed that plasticity window of mESCs is associated with the bivalent energetic metabolism and potency to shift to glycolysis or OXPHOS on demand. LIF removal provokes glycolytic metabolic orientation and consecutive loss of the LIF‐dependent reversion of cells to the pluripotent state. Stem Cells2019;37:463–475 Murine embryonic stem cells, pluripotent with leukemia inhibitory factor (LIF), are induced to differentiate by removing LIF for the times indicated in hours. The metabolic status of cells is indicated along with their properties. The switch toward “glycolysis mainly” status is associated with irreversible LIF‐dependent commitment of cells and loss of plasticity during this early time window.
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- 2019
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5. Energy Metabolism Rewiring Precedes UVB-Induced Primary Skin Tumor Formation
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Hosseini, Mohsen, Dousset, Léa, Mahfouf, Walid, Serrano-Sanchez, Martin, Redonnet-Vernhet, Isabelle, Mesli, Samir, Kasraian, Zeinab, Obre, Emilie, Bonneu, Marc, Claverol, Stephane, Vlaski, Marija, Ivanovic, Zoran, Rachidi, Walid, Douki, Thierry, Taieb, Alain, Bouzier-Sore, Anne-Karine, Rossignol, Rodrigue, and Rezvani, Hamid Reza
- Abstract
Although growing evidence indicates that bioenergetic metabolism plays an important role in the progression of tumorigenesis, little information is available on the contribution of reprogramming of energy metabolism in cancer initiation. By applying a quantitative proteomic approach and targeted metabolomics, we find that specific metabolic modifications precede primary skin tumor formation. Using a multistage model of ultraviolet B (UVB) radiation-induced skin cancer, we show that glycolysis, tricarboxylic acid (TCA) cycle, and fatty acid β-oxidation are decreased at a very early stage of photocarcinogenesis, while the distal part of the electron transport chain (ETC) is upregulated. Reductive glutamine metabolism and the activity of dihydroorotate dehydrogenase (DHODH) are both necessary for maintaining high ETC. Mice with decreased DHODH activity or impaired ETC failed to develop pre-malignant and malignant lesions. DHODH activity represents a major link between DNA repair efficiency and bioenergetic patterning during skin carcinogenesis.
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- 2018
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6. Redox Homeostasis and Mitochondrial Dynamics.
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Willems, Peter H.G.M., Rossignol, Rodrigue, Dieteren, Cindy E.J., Murphy, Michael P., and Koopman, Werner J.H.
- Abstract
Within living cells, mitochondria are considered relevant sources of reactive oxygen species (ROS) and are exposed to reactive nitrogen species (RNS). During the last decade, accumulating evidence suggests that mitochondrial (dys)function, ROS/RNS levels, and aberrations in mitochondrial morphology are interconnected, albeit in a cell- and context-dependent manner. Here it is hypothesized that ROS and RNS are involved in the short-term regulation of mitochondrial morphology and function via non-transcriptional pathways. We review the evidence for such a mechanism and propose that it allows homeostatic control of mitochondrial function and morphology by redox signaling. [ABSTRACT FROM AUTHOR]
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- 2015
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7. Cytopathies mitochondriales et anesthésie
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Nouette-Gaulain, Karine, Robin, Florian, Semjen, François, Obre, Émilie, Bellance, Nadège, Biais, Matthieu, and Rossignol, Rodrigue
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Les cytopathies mitochondriales sont des maladies rares pour lesquelles les enfants atteints sont soumis à des anesthésies répétées, dans le cadre d’une prise en charge de leur pathologie ou de l’urgence. Les agents de l’anesthésie présentent de nombreuses interactions avec le métabolisme mitochondrial, notamment les anesthésiques locaux, les agents halogénés et le propofol. De ce fait, il paraît essentiel de parfaitement connaître les malades suspects dès la consultation d’anesthésie afin d’optimiser les protocoles d’anesthésie et de prévenir les complications périopératoire. Les décompensations métaboliques à type d’acidose lactique, cardiorespiratoires et neurologiques sont à surveiller.
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- 2016
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8. Cannabinoid control of brain bioenergetics: Exploring the subcellular localization of the CB1 receptor.
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Hebert-Chatelain, Etienne, Reguero, Leire, Puente, Nagore, Lutz, Beat, Chaouloff, Francis, Rossignol, Rodrigue, Piazza, Pier-Vincenzo, Benard, Giovanni, Grandes, Pedro, and Marsicano, Giovanni
- Abstract
Abstract: Brain mitochondrial activity is centrally involved in the central control of energy balance. When studying mitochondrial functions in the brain, however, discrepant results might be obtained, depending on the experimental approaches. For instance, immunostaining experiments and biochemical isolation of organelles expose investigators to risks of false positive and/or false negative results. As an example, the functional presence of cannabinoid type 1 (CB
1 ) receptors on brain mitochondrial membranes (mtCB1 ) was recently reported and rapidly challenged, claiming that the original observation was likely due to artifact results. Here, we addressed this issue by directly comparing the procedures used in the two studies. Our results show that the use of appropriate controls and quantifications allows detecting mtCB1 receptor with CB1 receptor antibodies, and that, if mitochondrial fractions are enriched and purified, CB1 receptor agonists reliably decrease respiration in brain mitochondria. These data further underline the importance of adapted experimental procedures to study brain mitochondrial functions. [Copyright &y& Elsevier]- Published
- 2014
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9. Rheb Regulates Mitophagy Induced by Mitochondrial Energetic Status.
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Melser, Su, Chatelain, Etienne Hébert, Lavie, Julie, Mahfouf, Walid, Jose, Caroline, Obre, Emilie, Goorden, Susan, Priault, Muriel, Elgersma, Ype, Rezvani, Hamid Reza, Rossignol, Rodrigue, and Bénard, Giovanni
- Abstract
Summary: Mitophagy has been recently described as a mechanism of elimination of damaged organelles. Although the regulation of the amount of mitochondria is a core issue concerning cellular energy homeostasis, the relationship between mitochondrial degradation and energetic activity has not yet been considered. Here, we report that the stimulation of mitochondrial oxidative phosphorylation enhances mitochondrial renewal by increasing its degradation rate. Upon high oxidative phosphorylation activity, we found that the small GTPase Rheb is recruited to the mitochondrial outer membrane. This mitochondrial localization of Rheb promotes mitophagy through a physical interaction with the mitochondrial autophagic receptor Nix and the autophagosomal protein LC3-II. Thus, Rheb-dependent mitophagy contributes to the maintenance of optimal mitochondrial energy production. Our data suggest that mitochondrial degradation contributes to a bulk renewal of the organelle in order to prevent mitochondrial aging and to maintain the efficiency of oxidative phosphorylation. [Copyright &y& Elsevier]
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- 2013
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10. Modification of mitochondrial metabolism in fibroblasts from mice with a skeletal muscle mutation (muscular dysgenesis).
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Joffroy, Sandra, Letellier, Thierry, Rossignol, Rodrigue, Malgat, Monique, Delage, Jean-Paul, Powell, Jeanne A., Mazat, Jean-Pierre, and Koenig, Jeanine
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MUSCLE diseases ,MITOCHONDRIAL pathology ,NEUROMUSCULAR diseases ,METABOLISM ,MYOFIBROBLASTS ,MYOSITIS - Abstract
Muscle development during enthryogenesis is a complex pcocess involving many mechanisms. It requires a close communication among the differettt cellular types of the muscle, especially the fibroblasts and myoblasts. Indeed, any abnormality in one cell type might influence the differentiation of the other. Thus, any disturbance altering the metabolism of the myoblasts might lead to modifications in the fibroblasts. To study this phenomenon, we used the dysgenic mouse (mdg-"muscular dysgenesis") carrying a homozygous recessive lethal mutation expressed only in skeletal muscle cells. First, we found that fibroblasts isolated from such mutant muscle (and not from mutant skin tissue) and grown in culture exhibited an altered metabolism. Secondly, muscle fibroblasts showed a lower capacity for proliferation We also observed that respiration and ATP synthesis of dysgenic muscle fibroblasts were deficient, while respiratory chain enzymatic activities were normal. Finally, intracellular [Ca
2+ ] levels of dysgenic fibroblasts are 50% of those of normal fibroblasts. These results support the hypothesis that certain characteristics of fibroblasts are determined by the surrounding cellular environment during embryonic onganogenesis, and that such modifications are stable when the fibroblasts are isolated in vitro. Since fibroblast differentiation was disrupted permanently, this suggests, in the case of myopathies, that the modified cells, surrounding the muscle tissue, could contribute to the muscle pathology. Synergistic activities of this type should he considered when studying the course of pathologies in different types of muscle diseases. [ABSTRACT FROM AUTHOR]- Published
- 2000
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11. Local anesthetic ‘in-situ’ toxicity during peripheral nerve blocks
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Nouette-Gaulain, Karine, Capdevila, Xavier, and Rossignol, Rodrigue
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Peripheral nerve blocks induce undesired side-effects linked to the toxicity of local anesthetics on neuron and myocytes via different cell targets. The effects of local anesthetics on these targets are now well known and summarized in this review.
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- 2012
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12. Apoptotic-like mitochondrial events associated to phosphatidylserine exposure in blood platelets induced by local anaesthetics
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Augereau, Olivier, Rossignol, Rodrigue, DeGiorgi, Francesca, Mazat, Jean-Pierre, Letellier, Thierry, and Dachary-Prigent, Jeanne
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- 2004
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13. Mitochondrial threshold effects
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ROSSIGNOL, Rodrigue, FAUSTIN, Benjamin, ROCHER, Christophe, MALGAT, Monique, MAZAT, Jean-Pierre, and LETELLIER, Thierry
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The study of mitochondrial diseases has revealed dramatic variability in the phenotypic presentation of mitochondrial genetic defects. To attempt to understand this variability, different authors have studied energy metabolism in transmitochondrial cell lines carrying different proportions of various pathogenic mutations in their mitochondrial DNA. The same kinds of experiments have been performed on isolated mitochondria and on tissue biopsies taken from patients with mitochondrial diseases. The results have shown that, in most cases, phenotypic manifestation of the genetic defect occurs only when a threshold level is exceeded, and this phenomenon has been named the ‘phenotypic threshold effect'. Subsequently, several authors showed that it was possible to inhibit considerably the activity of a respiratory chain complex, up to a critical value, without affecting the rate of mitochondrial respiration or ATP synthesis. This phenomenon was called the ‘biochemical threshold effect'. More recently, quantitative analysis of the effects of various mutations in mitochondrial DNA on the rate of mitochondrial protein synthesis has revealed the existence of a ‘translational threshold effect'. In this review these different mitochondrial threshold effects are discussed, along with their molecular bases and the roles that they play in the presentation of mitochondrial diseases.
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- 2003
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14. Simple Models of Threshold Curves in the Expression of Inborn Errors of Metabolism: Application to some Experimental Observations
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Mazat, Jean-Pierre, Rossignol, Rodrigue, Malgat, Monique, and Letellier, Thierry
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The expression of an enzymatic deficiency in a metabolic network can present a biochemical threshold. This threshold can be characterised thus: (1) a low activity of the enzyme can sustain a normal flux, but (2) a minute further decrease of its activity makes the flux collapse. We give simple mathematical models displaying such a behaviour, and we apply the models to some examples of oxidative phosphorylation dependency on respiratory chain complex deficiency.
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- 2000
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15. Tissue variation in the control of oxidative phosphorylation: implication for mitochondrial diseases
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ROSSIGNOL, Rodrigue, LETELLIER, Thierry, MALGAT, Monique, ROCHER, Christophe, and MAZAT, Jean-Pierre
- Abstract
Metabolic control analysis has often been used for quantitative studies of the regulation of mitochondrial oxidative phosphorylations (OXPHOS). The main contribution of this work has been to show that the control of mitochondrial metabolic fluxes can be shared among several steps of the oxidative phosphorylation process, and that this distribution can vary according to the steady state and the tissue. However, these studies do not show whether this observed variation in the OXPHOS control is due to the experimental conditions or to the nature of the mitochondria. To find out if there actually exists a tissue variation in the distribution of OXPHOS control coefficients, we determined the control coefficients of seven OXPHOS complexes on the oxygen-consumption flux in rat mitochondria isolated from five different tissues under identical experimental conditions. Thus in this work, only the nature of the mitochondria can be responsible for any variation detected in the control coefficient values between different tissues. The analysis of control coefficient distribution shows two tissue groups: (i) the muscle and the heart, controlled essentially at the level of the respiratory chain; and (ii) the liver, the kidney and the brain, controlled mainly at the phosphorylation level by ATP synthase and the phosphate carrier. We propose that this variation in control coefficient according to the tissue origin of the mitochondria can explain part of the tissue specificity observed in mitochondrial cytopathies.
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- 2000
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16. Threshold Effect and Tissue Specificity
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Rossignol, Rodrigue, Malgat, Monique, Mazat, Jean-Pierre, and Letellier, Thierry
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Mitochondrial cytopathies present a tissue specificity characterized by the fact that even if a mitochondrial DNA mutation is present in all tissues, only some will be affected and induce a pathology. Several mechanisms have been proposed to explain this phenomenon such as the appearance of a sporadic mutation in a given stem cell during embryogenesis or mitotic segregation, giving different degrees of heteroplasmy in tissues. However, these mechanisms cannot be the only ones involved in tissue specificity. In this paper, we propose an additional mechanism contributing to tissue specificity. It is based on the metabolic expression of the defect in oxidative phosphorylation (OXPHOS) complexes that can present a biochemical threshold. The value of this threshold for a given OXPHOS complex can vary according to the tissue; thus different tissues will display different sensitivities to a defect in an OXPHOS complex. To verify this hypothesis and to illustrate the pathological consequences of the variation in biochemical thresholds, we studied their values for seven OXPHOS complexes in mitochondria isolated from five different rat tissues. Two types of behavior in the threshold curves can be distinguished corresponding to two modes of OXPHOS response to a deficiency. We propose a classification of tissues according to their type of OXPHOS response to a complex deficiency and therefore to their threshold values.
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- 1999
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17. Metabolic control, analysis and mitochondrial pathologies
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Letellier, Thierry, Malgat, Monique, Rossignol, Rodrigue, and Mazat, Jean-Pierre
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One of the main salient features recognized in mitochondrial diseases is the existence of a threshold in the degree of a mitochondrial deficit for the expression of the disease. When expressed as a function of the degree of heteroplasmy, the value of the threshold can be very high, around 90% (mutated DNA/total DNA). This means that 10% of normal DNA is enough to sustain a quasi normal mitochondrial oxidative phosphorylating flux. We have shown that most of the compensation is done at the metabolic level: for instance a 70% deficit of cytochrome oxidase decreases the oxidative flux by just 10%. Similar patterns are observed for the other complexes. Using Metabolic Control Anlaysis (MCA), we have shown that this kind of result is inescapable: the threshold value can be correlated to the control coefficient of the deficient step. The value of the threshold is reinforced by slight increases at the transcriptional and translational level as we show in a simple mathematical model. Finally we associate the threshold in the expression of a deficit, to the threshold in the energy demand of different tissues, in order to describe various patterns of onset of mitochondrial diseases (double threshold hypothesis).
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- 1998
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18. PML-Regulated Mitochondrial Metabolism Enhances Chemosensitivity in Human Ovarian Cancers.
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Gentric, Géraldine, Kieffer, Yann, Mieulet, Virginie, Goundiam, Oumou, Bonneau, Claire, Nemati, Fariba, Hurbain, Ilse, Raposo, Graca, Popova, Tatiana, Stern, Marc-Henri, Lallemand-Breitenbach, Valérie, Müller, Sebastian, Cañeque, Tatiana, Rodriguez, Raphaël, Vincent-Salomon, Anne, de Thé, Hugues, Rossignol, Rodrigue, and Mechta-Grigoriou, Fatima
- Abstract
Summary High-grade serous ovarian cancer (HGSOC) remains an unmet medical challenge. Here, we unravel an unanticipated metabolic heterogeneity in HGSOC. By combining proteomic, metabolomic, and bioergenetic analyses, we identify two molecular subgroups, low- and high-OXPHOS. While low-OXPHOS exhibit a glycolytic metabolism, high-OXPHOS HGSOCs rely on oxidative phosphorylation, supported by glutamine and fatty acid oxidation, and show chronic oxidative stress. We identify an important role for the PML-PGC-1α axis in the metabolic features of high-OXPHOS HGSOC. In high-OXPHOS tumors, chronic oxidative stress promotes aggregation of PML-nuclear bodies, resulting in activation of the transcriptional co-activator PGC-1α. Active PGC-1α increases synthesis of electron transport chain complexes, thereby promoting mitochondrial respiration. Importantly, high-OXPHOS HGSOCs exhibit increased response to conventional chemotherapies, in which increased oxidative stress, PML, and potentially ferroptosis play key functions. Collectively, our data establish a stress-mediated PML-PGC-1α-dependent mechanism that promotes OXPHOS metabolism and chemosensitivity in ovarian cancer. Graphical Abstract Highlights • High-grade serous ovarian cancers display OXPHOS metabolic heterogeneity • High-OXPHOS show high electron transport chain synthesis and respiration rate • Oxidative stress in high-OXPHOS HGSOC activates PML-PGC-1α and ETC transcription • High-OXPHOS HGSOCs show enhanced chemosensitivity through oxidative stress and PML Gentric et al. identify metabolically heterogeneous OXPHOS subgroups in high-grade serous ovarian cancers (HGSOCs). In high-OXPHOS tumors, chronic oxidative stress promotes aggregation of PML-nuclear bodies that activate PGC-1α, electron transport chain synthesis, and mitochondrial respiration. High-OXPHOS HGSOCs exhibit chemosensitivity, in which increased oxidative stress and PML play key functions. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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19. Studying mitochondrial CB1 receptors: Yes we can.
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Hebert-Chatelain, Etienne, Reguero, Leire, Puente, Nagore, Lutz, Beat, Chaouloff, Francis, Rossignol, Rodrigue, Piazza, Pier-Vincenzo, Benard, Giovanni, Grandes, Pedro, and Marsicano, Giovanni
- Published
- 2014
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20. La lévobupivacaïne inhibe la prolifération in vitro des cellules de carcinome épidermoïde humain et altère le métabolisme énergétique cellulaire
- Author
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Robin, Florian, Rossignol, Rodrigue, Obre, Emilie, Hamonic, Yann, and Nouette-Gaulain, Karine
- Abstract
Sur modèle murin, l’infiltration prolongée de lévobupivacaïne après chirurgie d’exérèse de tumeurs de type spinocellulaires réduit la taille des récidives tumorales [1]. L’objectif de ce travail consiste à confirmer in vitro la cytotoxicité de la lévobupivacaïne sur un modèle cellulaire de carcinome épidermoïde humain et d’étudier les mécanismes métaboliques impliqués dans l’interaction entre la lévobupivacaïne et les cellules cancéreuses.
- Published
- 2015
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