Acetylation of Yeast AMPK Controls Intrinsic Aging Independently of Caloric Restriction

作者：Lu Jin Ying; Lin Yu Yi; Sheu Jin Chuan; Wu June Tai; Lee Fang Jen; Chen Yue; Lin Min I; Chiang Fu Tien; Tai Tong Yuan; Berger Shelley L; Zhao Yingming; Tsai Keh Sung; Zhu Heng^*; Chuang Lee Ming; Boeke Jef D

来源：Cell, 2011, 146(6): 968-978.

DOI：10.1016/j.cell.2011.07.044

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.

• 出版日期2011-9-16