Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China; The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China; State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, The Chinese Academy of Sciences, Beijing, 100101, China.
Department of Chemistry and Biology, National University of Defense Technology, Changsha, 410072, China.
J Genet Genomics. 2019 Apr 20;46(4):221-229. doi: 10.1016/j.jgg.2019.03.008. Epub 2019 Apr 21.
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.
自噬作为一种适应细胞的过程，已经进化到可以响应各种应激，如营养缺乏。各种细胞货物，如受损的细胞器和蛋白质聚集体，可以通过自噬被选择性降解。最近，脂质储存细胞器，脂滴（LD），被报道为饥饿诱导自噬的货物。然而，自噬机制如何识别 LD，以及它是否能选择性地降解 LD，在很大程度上仍然未知。在这项研究中，我们表明果蝇组蛋白去乙酰化酶 6（dHDAC6），选择性自噬的关键调节因子，在饥饿响应中，类肝细胞的性腺细胞中 LD 的周转是必需的。HDAC6 通过 p62/SQSTM1（自噬体相关蛋白 1）介导的聚集体形成来调节 LD 的周转，这表明选择性自噬机制是 LD 识别和降解所必需的。此外，我们的结果表明，dHDAC6 的缺失会导致饥饿时的脂肪变性。我们的研究结果表明，在应激条件下，选择性自噬与易患与脂质代谢相关疾病的易感性之间可能存在联系。
