State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing, China.
Science. 2012 Apr 27;336(6080):474-7. doi: 10.1126/science.1216990.
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.
蛋白质乙酰化作用已成为许多细胞过程的关键调节机制。我们使用酿酒酵母的遗传分析来鉴定 Esa1 是一种自噬所必需的组蛋白乙酰转移酶。我们进一步鉴定了自噬信号成分 Atg3 是 Esa1 的底物。具体而言，Atg3 的 K19 和 K48 的乙酰化通过控制 Atg3 和 Atg8 相互作用以及 Atg8 的脂质化来调节自噬。通过空间和时间调节乙酰转移酶 Esa1 和去乙酰化酶 Rpd3 在前自噬体结构（PAS）上的定位及其与 Atg3 的相互作用，饥饿诱导了 Atg3 的瞬时 K19-K48 乙酰化。K19-K48 乙酰化的减弱与自噬的减弱有关。删除去乙酰化酶 Rpd3 后 K19-K48 乙酰化增加会导致自噬增加。因此，蛋白质乙酰化有助于控制自噬。
