Role of PGC-1α signaling in skeletal muscle health and disease

This paper reviews the current understanding of the molecular basis of the peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α)–mediated pathway and discusses the role of PGC‐1α in skeletal muscle atrophy caused by immobilization. PGC‐1α is the master transcription regulator that stimulates mitochondrial biogenesis, by upregulating nuclear respiratory factors (NRF‐1, 2) and mitochondrial transcription factor A (Tfam), which leads to increased mitochondrial DNA replication and gene transcription. PGC‐1α also regulates cellular oxidant–antioxidant homeostasis by stimulating the gene expression of superoxide dismutase‐2 (SOD2), catalase, glutathione peroxidase 1 (GPx1), and uncoupling protein (UCP). Recent reports from muscle‐specific PGC‐1α overexpression underline the importance of PGC‐1α in atrophied skeletal muscle, demonstrate enhancement of the PGC‐1α mitochondrial biogenic pathway, and reduced oxidative damage. Thus, PGC‐1α appears to play a protective role against atrophy‐linked skeletal muscle deterioration.