title: The transcriptional coregulator PGC-1β controls mitochondrial function and anti-oxidant defence in skeletal muscles.
abstract: 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.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique UMR 7104, Institut National de la Santé et de la Recherche Médicale U964, Université de Strasbourg, 67400 Illkirch, France.
authors.forename: Thanuja
authors.initials: T
authors.lastname: Gali Ramamoorthy
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique UMR 7104, Institut National de la Santé et de la Recherche Médicale U964, Université de Strasbourg, 67400 Illkirch, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Laverny
authors.affiliation: Institut de Physiologie EA 3072, Fédération de Médecine Translationnelle, Université de Strasbourg, Service de physiologie et d'Explorations Fonctionnelles, CHRU, 67000 Strasbourg, France.
authors.forename: Anna-Isabel
authors.initials: AI
authors.lastname: Schlagowski
authors.affiliation: Institut de Physiologie EA 3072, Fédération de Médecine Translationnelle, Université de Strasbourg, Service de physiologie et d'Explorations Fonctionnelles, CHRU, 67000 Strasbourg, France.
authors.forename: Joffrey
authors.initials: J
authors.lastname: Zoll
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique UMR 7104, Institut National de la Santé et de la Recherche Médicale U964, Université de Strasbourg, 67400 Illkirch, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Messaddeq
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique UMR 7104, Institut National de la Santé et de la Recherche Médicale U964, Université de Strasbourg, 67400 Illkirch, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Bornert
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique UMR 7104, Institut National de la Santé et de la Recherche Médicale U964, Université de Strasbourg, 67400 Illkirch, France.|Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panza
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U974, Centre National de la Recherche Scientifique UMR 7215, Université Pierre et Marie Curie-Paris 6 and Université Paris Descartes, 75006 Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Ferry
authors.affiliation: Institut de Physiologie EA 3072, Fédération de Médecine Translationnelle, Université de Strasbourg, Service de physiologie et d'Explorations Fonctionnelles, CHRU, 67000 Strasbourg, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Geny
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique UMR 7104, Institut National de la Santé et de la Recherche Médicale U964, Université de Strasbourg, 67400 Illkirch, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
mesh_terms: D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D018274:Electroporation; D005080:Exercise Test; D005609:Free Radicals / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D005951:Glucose Tolerance Test; D018737:Hand Strength / Q000502:physiology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D015227:Lipid Peroxidation; D051379:Mice; D008931:Mitochondria, Muscle / Q000378:metabolism*; D009119:Muscle Contraction / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D053580:Muscle Strength / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D032446:Myoblasts / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D005609:Free Radicals; D006861:Hydrogen Peroxide; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2; C485290:Ppargc1a protein, mouse