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

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

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 Fibers, Skeletal / pathology
  • Muscle Fibers, Skeletal / physiology
  • Muscle Strength / genetics
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiology
  • Myoblasts / metabolism*
  • Oxidative Stress / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • RNA, Messenger / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Free Radicals
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • RNA, Messenger
  • Reactive Oxygen Species
  • Transcription Factors
  • Hydrogen Peroxide
  • Superoxide Dismutase
  • superoxide dismutase 2

Associated data

  • GEO/GSE73572