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

This paper reviews the current understanding of the molecular basis of the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha)-mediated pathway and discusses the role of PGC-1 alpha in skeletal muscle atrophy caused by immobilization. PGC-1 alpha 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-1 alpha 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-1 alpha overexpression underline the importance of PGC-1 alpha in atrophied skeletal muscle, demonstrate enhancement of the PGC-1 alpha mitochondrial biogenic pathway, and reduced oxidative damage. Thus, PGC-1 alpha appears to play a protective role against atrophy-linked skeletal muscle deterioration.