HDAC6 regulates lipid droplet turnover in response to nutrient deprivation via p62-mediated selective autophagy
HDAC6 regulates lipid droplet turnover in response to nutrient deprivation via p62-mediated selective autophagy
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HDAC6 通过 p62 介导的选择性自噬调节脂滴周转以响应营养剥夺
DOI：
10.1016/j.jgg.2019.03.008
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发表时间：
2019-04-20
影响因子：
5.9
通讯作者：
Jiao, Renjie
中科院分区：
文献类型：
--
作者：
Yan, Yan;Wang, Hao;Jiao, Renjie
自噬是细胞对营养缺乏等应激反应的一种适应性过程。各种细胞货物，如受损的细胞器和蛋白质聚集体可以通过自噬选择性降解。最近，脂质储存细胞器，脂滴（LD），已被报道是饥饿诱导的自噬的货物。然而，自噬机制如何识别LD以及它是否可以选择性降解LD仍然是未知的。在这项研究中，我们表明果蝇组蛋白脱乙酰酶6（dHDAC 6）是选择性自噬的关键调节因子，是肝细胞样酒细胞响应饥饿的LD周转所必需的。HDAC 6通过p62/SQSTM 1（隔离体1）介导的侵袭体形成调节LD周转，表明LD识别和降解需要选择性自噬机制。此外，我们的研究结果表明，dHDAC 6的损失导致脂肪变性，响应于饥饿。我们的研究结果表明，在应激条件下，选择性自噬与脂质代谢相关疾病的易感性之间存在潜在联系。中国科学院遗传与发育生物学研究所、中国遗传学会版权所有（C）2019。由爱思唯尔有限公司和科学出版社出版。All rights reserved.
Autophagy has been evolved as one of the adaptive cellular processes in response to stresses such as nutrient deprivation. Various cellular cargos such as damaged organelles and protein aggregates can be selectively degraded through autophagy. Recently, the lipid storage organelle, lipid droplet (LD), has been reported to be the cargo of starvation-induced autophagy. However, it remains largely unknown how the autophagy machinery recognizes the LDs and whether it can selectively degrade LDs. In this study, we show that Drosophila histone deacetylase 6 (dHDAC6), a key regulator of selective autophagy, is required for the LD turnover in the hepatocyte-like oenocytes in response to starvation. HDAC6 regulates LD turnover via p62/SQSTM1 (sequestosome 1)-mediated aggresome formation, suggesting that the selective autophagy machinery is required for LD recognition and degradation. Furthermore, our results show that the loss of dHDAC6 causes steatosis in response to starvation. Our findings suggest that there is a potential link between selective autophagy and susceptible predisposition to lipid metabolism associated diseases in stress conditions. Copyright (C) 2019, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.