Fiche publication
Date publication
décembre 2015
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr METZGER Daniel
,
Dr LAVERNY Gilles
,
Mme MESSADDEQ Nadia
,
Pr GENY Bernard
Tous les auteurs :
Gali Ramamoorthy T, Laverny G, Schlagowski AI, Zoll J, Messaddeq N, Bornert JM, Panza S, Ferry A, Geny B, Metzger D
Lien Pubmed
Résumé
The transcriptional coregulators PGC-1α and PGC-1β modulate the expression of numerous partially overlapping genes involved in mitochondrial biogenesis and energetic metabolism. The physiological role of PGC-1β is poorly understood in skeletal muscle, a tissue of high mitochondrial content to produce ATP levels required for sustained contractions. Here we determine the physiological role of PGC-1β in skeletal muscle using mice, in which PGC-1β is selectively ablated in skeletal myofibres at adulthood (PGC-1β((i)skm-/-) mice). We show that myofibre myosin heavy chain composition and mitochondrial number, muscle strength and glucose homeostasis are unaffected in PGC-1β((i)skm-/-) mice. However, decreased expression of genes controlling mitochondrial protein import, translational machinery and energy metabolism in PGC-1β((i)skm-/-) muscles leads to mitochondrial structural and functional abnormalities, impaired muscle oxidative capacity and reduced exercise performance. Moreover, enhanced free-radical leak and reduced expression of the mitochondrial anti-oxidant enzyme Sod2 increase muscle oxidative stress. PGC-1β is therefore instrumental for skeletal muscles to cope with high energetic demands.
Mots clés
Animals, Electron Spin Resonance Spectroscopy, Electroporation, Exercise Test, Free Radicals, metabolism, Gene Expression Profiling, Gene Expression Regulation, Gene Knockout Techniques, Glucose Tolerance Test, Hand Strength, physiology, Hydrogen Peroxide, metabolism, Insulin Resistance, genetics, Lipid Peroxidation, Mice, Mitochondria, Muscle, metabolism, Muscle Contraction, genetics, Muscle Fibers, Skeletal, metabolism, Muscle Strength, genetics, Muscle, Skeletal, metabolism, Myoblasts, metabolism, Oxidative Stress, genetics, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, RNA, Messenger, metabolism, Reactive Oxygen Species, metabolism, Superoxide Dismutase, genetics, Transcription Factors, genetics
Référence
Nat Commun. 2015 Dec;6:10210
