Acetylation of Yeast AMPK Controls Intrinsic Aging Independently of Caloric Restriction

Cell. 2011 Sep 16;146(6):969-79. doi: 10.1016/j.cell.2011.07.044. Epub 2011 Sep 9.

Abstract

Acetylation of histone and nonhistone proteins is an important posttranslational modification affecting many cellular processes. Here, we report that NuA4 acetylation of Sip2, a regulatory β subunit of the Snf1 complex (yeast AMP-activated protein kinase), decreases as cells age. Sip2 acetylation, controlled by antagonizing NuA4 acetyltransferase and Rpd3 deacetylase, enhances interaction with Snf1, the catalytic subunit of Snf1 complex. Sip2-Snf1 interaction inhibits Snf1 activity, thus decreasing phosphorylation of a downstream target, Sch9 (homolog of Akt/S6K), and ultimately leading to slower growth but extended replicative life span. Sip2 acetylation mimetics are more resistant to oxidative stress. We further demonstrate that the anti-aging effect of Sip2 acetylation is independent of extrinsic nutrient availability and TORC1 activity. We propose a protein acetylation-phosphorylation cascade that regulates Sch9 activity, controls intrinsic aging, and extends replicative life span in yeast.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Acetylation
  • Caloric Restriction
  • Cell Division
  • Histone Acetyltransferases / metabolism
  • Histone Deacetylases / metabolism
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism

Substances

  • SIP2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • TORC1 protein complex, S cerevisiae
  • Trans-Activators
  • Transcription Factors
  • Histone Acetyltransferases
  • NuA4 protein, S cerevisiae
  • Protein Kinases
  • SCH9 protein kinase
  • SNF1-related protein kinases
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • RPD3 protein, S cerevisiae
  • Histone Deacetylases