Deacetylation of PGC-1α by SIRT1: importance for skeletal muscle function and exercise-induced mitochondrial biogenesis.Appl Physiol Nutr Metab 2011; 36(5):589-97AP
Activation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-mediated transcription is important for both the determination of mitochondrial content and the induction of mitochondrial biogenesis in skeletal muscle. SIRT1 (silent mating type information regulator 2 homolog 1) deactetylation is proposed as a potential activator of PGC-1α transcriptional activity. The current review examines the importance of SIRT1 deacetylation of PGC-1α in skeletal muscle. Models of SIRT1 overexpression and pharmacological activation are examined, but changes in SIRT1 expression and deacetylase activity following acute and chronic contractile activity will be emphasized. In addition, potential mechanisms of SIRT1 activation in skeletal muscle will be examined. The importance of the PGC-1α acetyltransferase GCN5 will also be briefly discussed. The current evidence supports the contribution of SIRT1 deacetylation of PGC-1α to exercise-induced mitochondrial biogenesis. Further research examining exercise-mediated activation of SIRT1 and the role of GCN5 in regulating PGC-1α transcriptional activity in skeletal muscle is required.