Protein acetylation emerged as a key regulatory mechanism for many cellular processes. We used genetic analysis of Saccharomyces cerevisiae to identify Esa1 as a histone acetyltransferase required for autophagy. We further identified the autophagy signaling component Atg3 as a substrate for Esa1. Specifically, acetylation of K19 and K48 of Atg3 regulated autophagy by controlling Atg3 and Atg8 interaction and lipidation of Atg8. Starvation induced transient K19-K48 acetylation through spatial and temporal regulation of the localization of acetylase Esa1 and the deacetylase Rpd3 on pre-autophagosomal structures (PASs) and their interaction with Atg3. Attenuation of K19-K48 acetylation was associated with attenuation of autophagy. Increased K19-K48 acetylation after deletion of the deacetylase Rpd3 caused increased autophagy. Thus, proteinacetylation contributes to control of autophagy.

Yi C, Ma MS, Ran LL, Zheng JX, Tong JJ, Zhu J, Ma CY, Sun YF, Zhang SJ, Feng WZ, Zhu LY, Le Y, Gong XQ, Yan XH, Hong B, Jiang FJ, Xie ZP, Miao D, Deng H, Yu L*. (2012) Function and Molecular Mechanism of Acetylation in Autophagy Regulation. Science, 336(6080):474-477.