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.

自噬已经发展成为对压力（例如营养缺乏）的一种适应性细胞过程。各种细胞货物，例如受损的细胞器和蛋白质聚集体，可以通过自噬选择性地降解。近来，已经报道了脂质储存细胞器脂质滴（LD）是饥饿诱导的自噬的产物。但是，自噬机器如何识别LD以及能否选择性降解LD仍是一个未知数。在这项研究中，我们表明果蝇组蛋白脱乙酰基酶6（dHDAC6）是选择性自噬的关键调节剂，它是饥饿时肝细胞样细胞中LD转换所必需的。HDAC6通过p62 / SQSTM1（半定形体1）介导的聚集体形成调节LD周转率，表明LD识别和降解需要选择性自噬机制。此外，我们的结果表明，dHDAC6的丧失会导致饥饿引起脂肪变性。我们的发现表明，在应激条件下，选择性自噬与脂代谢相关疾病的易感性之间存在潜在的联系。