title: Acetylation of yeast AMPK controls intrinsic aging independently of caloric restriction.
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.
authors: Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University, Taipei 100, Taiwan.
authors: Jin-Ying
authors: JY
authors: Lu
authors: Yu-Yi
authors: YY
authors: Lin
authors: Jin-Chuan
authors: JC
authors: Sheu
authors: June-Tai
authors: JT
authors: Wu
authors: Fang-Jen
authors: FJ
authors: Lee
authors: Yue
authors: Y
authors: Chen
authors: Min-I
authors: MI
authors: Lin
authors: Fu-Tien
authors: FT
authors: Chiang
authors: Tong-Yuan
authors: TY
authors: Tai
authors: Shelley L
authors: SL
authors: Berger
authors: Yingming
authors: Y
authors: Zhao
authors: Keh-Sung
authors: KS
authors: Tsai
authors: Heng
authors: H
authors: Zhu
authors: Lee-Ming
authors: LM
authors: Chuang
authors: Jef D
authors: JD
authors: Boeke
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000107:Acetylation; D031204:Caloric Restriction; D002455:Cell Division; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C091267:SIP2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C561842:TORC1 protein complex, S cerevisiae; D015534:Trans-Activators; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C504740:NuA4 protein, S cerevisiae; D011494:Protein Kinases; C071569:SCH9 protein kinase; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases