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Nat Commun. 2015 Dec 17;6:10210. doi: 10.1038/ncomms10210.

The transcriptional coregulator PGC-1β controls mitochondrial function and anti-oxidant defence in skeletal muscles.

Author information

1
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.
2
Institut de Physiologie EA 3072, Fédération de Médecine Translationnelle, Université de Strasbourg, Service de physiologie et d'Explorations Fonctionnelles, CHRU, 67000 Strasbourg, France.
3
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, 87036 Cosenza, Italy.
4
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.

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.

PMID:
26674215
PMCID:
PMC4703903
DOI:
10.1038/ncomms10210
[Indexed for MEDLINE]
Free PMC Article

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