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Science 336 (6080): 474-477

Copyright © 2012 by the American Association for the Advancement of Science

Function and Molecular Mechanism of Acetylation in Autophagy Regulation

Cong Yi,1 Meisheng Ma,1 Leili Ran,1 Jingxiang Zheng,1 Jingjing Tong,1 Jing Zhu,1 Chengying Ma,2 Yufen Sun,1 Shaojin Zhang,1 Wenzhi Feng,1 Liyuan Zhu,1 Yan Le,1 Xingqi Gong,2 Xianghua Yan,3 Bing Hong,4 Fen-Jun Jiang,4 Zhiping Xie,4 Di Miao,5 Haiteng Deng,5 Li Yu1,*

Abstract: 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, protein acetylation contributes to control of autophagy.

1 State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University–Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
2 Center of Structural Biology, Tsinghua University, Beijing 100084, China.
3 College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
4 School of Medicine, Nankai University, 94 Wei-Jin Road, Tianjin 300071, China.
5 Proteomics Facility, School of Life Sciences, Tsinghua University, Beijing 100084, China.

* To whom correspondence should be addressed. E-mail: liyulab{at}

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