Hormonal
SIRT1 activation or overexpression increases PGC-1α gene transcription and mRNA expression in skeletal muscle cells through a mechanism involving direct binding to the PGC-1α promoter and interaction with the myogenic factor MyoD.
Skeletal muscle adaptation to metabolic demands involves SIRT1 regulating the expression of PGC-1α, a key master regulator of mitochondrial biogenesis. This process requires the interaction of SIRT1 with MyoD. While SIRT1 activators exist, their ability to increase PGC-1α transcription depends on the cellular environment and the presence of myogenic factors, suggesting that exercise (which induces MyoD and metabolic changes) is a critical co-factor for this pathway.
SIRT1 activation or overexpression in differentiated C2C12 myotubes increased PGC-1α mRNA expression. The transcription-promoting effects of SIRT1 occurred through stimulation of PGC-1α promoter activity and were enhanced by co-transfection of myogenic factors, such as myocyte enhancer factor 2 (MEF2) and, especially, myogenic determining factor (MyoD).
Why this rating
The study uses multiple complementary methods (SIRT1-null mice, adenoviral overexpression, promoter assays, ChIP, immunoprecipitation) in well-controlled cellular and animal models.
Source
SIRT1 Controls the Transcription of the Peroxisome Proliferator-activated Receptor-γ Co-activator-1α (PGC-1α) Gene in Skeletal Muscle through the PGC-1α Autoregulatory Loop and Interaction with MyoD
Ramon Amat et al. · Journal of Biological Chemistry · 2009
DOI 10.1074/jbc.m109.022749
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