The transcriptional coregulator PGC-1? controls mitochondrial function and anti-oxidant defence in skeletal muscles.
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ABSTRACT: The transcriptional coregulators PGC-1? and PGC-1? modulate the expression of numerous partially overlapping genes involved in mitochondrial biogenesis and energetic metabolism. The physiological role of PGC-1? 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-1? in skeletal muscle using mice, in which PGC-1? is selectively ablated in skeletal myofibres at adulthood (PGC-1?((i)skm-/-) mice). We show that myofibre myosin heavy chain composition and mitochondrial number, muscle strength and glucose homeostasis are unaffected in PGC-1?((i)skm-/-) mice. However, decreased expression of genes controlling mitochondrial protein import, translational machinery and energy metabolism in PGC-1?((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-1? is therefore instrumental for skeletal muscles to cope with high energetic demands.
SUBMITTER: Gali Ramamoorthy T
PROVIDER: S-EPMC4703903 | biostudies-literature | 2015 Dec
REPOSITORIES: biostudies-literature
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