Sirt1 and the Mitochondria

Mol Cells. 2016 Feb;39(2):87-95. doi: 10.14348/molcells.2016.2318. Epub 2016 Feb 2.


Sirt1 is the most prominent and extensively studied member of sirtuins, the family of mammalian class III histone deacetylases heavily implicated in health span and longevity. Although primarily a nuclear protein, Sirt1's deacetylation of Peroxisome proliferator-activated receptor Gamma Coactivator-1α (PGC-1α) has been extensively implicated in metabolic control and mitochondrial biogenesis, which was proposed to partially underlie Sirt1's role in caloric restriction and impacts on longevity. The notion of Sirt1's regulation of PGC-1α activity and its role in mitochondrial biogenesis has, however, been controversial. Interestingly, Sirt1 also appears to be important for the turnover of defective mitochondria by mitophagy. I discuss here evidences for Sirt1's regulation of mitochondrial biogenesis and turnover, in relation to PGC-1α deacetylation and various aspects of cellular physiology and disease.

Keywords: PGC-1α; Sirt1; mitochondria; mitochondrial biogenesis; mitophagy.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Caloric Restriction
  • Gene Expression Regulation
  • Humans
  • Longevity / genetics*
  • Mitochondria / metabolism*
  • Mitophagy
  • Organelle Biogenesis
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Signal Transduction
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Transcription Factors
  • AMP-Activated Protein Kinases
  • SIRT1 protein, human
  • Sirtuin 1