Regulation of skeletal muscle mitochondrial function by nuclear receptors: implications for health and disease

Clin Sci (Lond). 2015 Oct;129(7):589-99. doi: 10.1042/CS20150246.

Abstract

Skeletal muscle metabolism is highly dependent on mitochondrial function, with impaired mitochondrial biogenesis associated with the development of metabolic diseases such as insulin resistance and type 2 diabetes. Mitochondria display substantial plasticity in skeletal muscle, and are highly sensitive to levels of physical activity. It is thought that physical activity promotes mitochondrial biogenesis in skeletal muscle through increased expression of genes encoded in both the nuclear and the mitochondrial genome; however, how this process is co-ordinated at the cellular level is poorly understood. Nuclear receptors (NRs) are key signalling proteins capable of integrating environmental factors and mitochondrial function, thereby providing a potential link between exercise and mitochondrial biogenesis. The aim of this review is to highlight the function of NRs in skeletal muscle mitochondrial biogenesis and discuss the therapeutic potential of NRs for the management and treatment of chronic metabolic disease.

Keywords: DNA methylation; Epigenetics; Nuclear receptor; Transcription; exercise; mitochondrial function; non-communicable disease; nuclear receptor; skeletal muscle; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chickens
  • Diabetes Mellitus, Type 2 / metabolism
  • Exercise
  • Gene Expression Regulation*
  • Genome, Mitochondrial
  • Humans
  • Mice
  • Mitochondria / physiology*
  • Mitochondria, Muscle / physiology
  • Muscle, Skeletal / physiology*
  • Muscular Diseases / metabolism
  • Ovalbumin / metabolism
  • Peroxisome Proliferator-Activated Receptors / physiology
  • Physical Conditioning, Animal
  • Rats
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Receptors, Thyroid Hormone / physiology
  • Transcription Factors / physiology

Substances

  • Peroxisome Proliferator-Activated Receptors
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Thyroid Hormone
  • Transcription Factors
  • Ovalbumin