Energy sensing and regulation of gene expression in skeletal muscle

Major modifications in energy homeostasis occur in skeletal muscle during exercise. Emerging evidence suggests that changes in energy homeostasis take part in the regulation of gene expression and contribute to muscle plasticity. A number of energy-sensing molecules have been shown to sense variations in energy homeostasis and trigger regulation of gene expression. The AMP-activated protein kinase, hypoxia-inducible factor 1, peroxisome proliferator-activated receptors, and Sirt1 proteins all contribute to altering skeletal muscle gene expression by sensing changes in the concentrations of AMP, molecular oxygen, intracellular free fatty acids, and NAD(+), respectively. These molecules may therefore sense information relating to the intensity, duration, and frequency of muscle exercise. Mitochondria also contribute to the overall response, both by modulating the response of energy-sensing molecules and by generating their own signals. This review seeks to examine our current understanding of the roles that energy-sensing molecules and mitochondria can play in the regulation of gene expression in skeletal muscle.