Acetylation of yeast AMPK controls intrinsic aging independently of caloric restriction.

Authors: Lu JY; Lin YY; Sheu JC; Wu JT; Lee FJ; Chen Y; Lin MI; Chiang FT; Tai TY; Berger SL; Zhao Y; Tsai KS; Zhu H; Chuang LM; Boeke JD

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 beta 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.

Keywords: 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/enzymology/*physiology; Saccharomyces cerevisiae Proteins/*metabolism; Trans-Activators/*metabolism; Transcription Factors/metabolism
Journal: Cell
Volume: 146
Issue: 6
Pages: 969-79
Date: Sept. 13, 2011
PMID: 21906795
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Citation:

Lu JY, Lin YY, Sheu JC, Wu JT, Lee FJ, Chen Y, Lin MI, Chiang FT, Tai TY, Berger SL, Zhao Y, Tsai KS, Zhu H, Chuang LM, Boeke JD (2011) Acetylation of yeast AMPK controls intrinsic aging independently of caloric restriction. Cell 146: 969-79.


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