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.
School of Kinesiology, University of Minnesota, Minneapolis, MN, USA.
Chounghun
C
Kang
Li
L
Li Ji
D000375:Aging / Q000378:metabolism; D000818:Animals; D015444:Exercise; D015971:Gene Expression Regulation, Enzymologic; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D063269:Mitochondrial Turnover; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism*; D009133:Muscular Atrophy / Q000378:metabolism; D009140:Musculoskeletal Diseases / Q000276:immunology / Q000378:metabolism*; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*
D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D010088:Oxidoreductases