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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Electron Spin Resonance Spectroscopy
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Electroporation
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Exercise Test
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Free Radicals / metabolism
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Gene Expression Profiling
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Gene Expression Regulation*
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Gene Knockout Techniques
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Glucose Tolerance Test
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Hand Strength / physiology
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Hydrogen Peroxide / metabolism
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Insulin Resistance / genetics
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Lipid Peroxidation
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Mice
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Mitochondria, Muscle / metabolism*
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Muscle Contraction / genetics
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Muscle Fibers, Skeletal / metabolism
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Muscle Fibers, Skeletal / pathology
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Muscle Fibers, Skeletal / physiology
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Muscle Strength / genetics
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Muscle, Skeletal / metabolism*
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Muscle, Skeletal / pathology
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Muscle, Skeletal / physiology
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Myoblasts / metabolism*
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Oxidative Stress / genetics
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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RNA, Messenger / metabolism*
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Reactive Oxygen Species / metabolism*
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Superoxide Dismutase / genetics
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Superoxide Dismutase / metabolism
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Transcription Factors / genetics*
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Transcription Factors / metabolism
Substances
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Free Radicals
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Ppargc1a protein, mouse
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RNA, Messenger
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Reactive Oxygen Species
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Transcription Factors
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Hydrogen Peroxide
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Superoxide Dismutase
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superoxide dismutase 2