Deacetylation of Nuclear LC3 Drives Autophagy Initiation under Starvation
Deacetylation of Nuclear LC3 Drives Autophagy Initiation under Starvation
复制标题
饥饿条件下核 LC3 的脱乙酰化驱动自噬启动
DOI：
10.1016/j.molcel.2014.12.013
复制
发表时间：
2015-02-05
期刊：
影响因子：
16
通讯作者：
Liu, Wei
中科院分区：
文献类型：
--
作者：
Huang, Rui;Xu, Yinfeng;Liu, Wei
在不同的细胞隔间之间穿梭大分子有助于调节不同细胞活动的时间和程度。在这里，我们报道了在细胞核和细胞质之间循环的自噬的关键启动子Lc3在饥饿期间通过核去乙酰酶Sirt1选择性地在细胞核中被激活。Lc3在K49和K51位被Sirt1去乙酰化，使Lc3与核蛋白DOR相互作用，并与DOR一起返回细胞质，在那里它能够与ATG7和其他自噬因子结合，并与磷脂酰乙醇胺结合到自噬前膜上。去乙酰化的Lc3与自噬因子的结合使Lc3‘S的分布从胞核向胞质移动。因此，乙酰化-去乙酰化循环确保了LC3有效地以激活的形式从细胞核重新分布到细胞质，在自噬中发挥核心作用，使细胞能够应对外部营养的缺乏。
Shuttling of macromolecules between different cellular compartments helps regulate the timing and extent of different cellular activities. Here, we report that LC3, a key initiator of autophagy that cycles between the nucleus and cytoplasm, becomes selectively activated in the nucleus during starvation through deacetylation by the nuclear deacetylase Sirt1. Deacetylation of LC3 at K49 and K51 by Sirt1 allows LC3 to interact with the nuclear protein DOR and return to the cytoplasm with DOR, where it is able to bind Atg7 and other autophagy factors and undergo phosphatidylethanolamine conjugation to preautophagic membranes. The association of deacetylated LC3 with autophagic factors shifts LC3's distribution from the nucleus toward the cytoplasm. Thus, an acetylation-deacetylation cycle ensures that LC3 effectively redistributes in an activated form from nucleus to cytoplasm, where it plays a central role in autophagy to enable the cell to cope with the lack of external nutrients.