The lipid flippase Drs2 regulates anterograde transport of Atg9 during autophagy.

Franziska Kriegenburg, Wouter Huiting, Fleur van Buuren-Broek, Emma Zwilling, Ralph Hardenberg, Muriel Mari, Claudine Kraft, Fulvio Reggiori
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Abstract

Macroautophagy/autophagy is a conserved catabolic pathway during which cellular material is sequestered within newly formed double-membrane vesicles called autophagosomes and delivered to the lytic compartment of eukaryotic cells for degradation. Autophagosome biogenesis depends on the core autophagy-related (Atg) machinery, and involves a massive supply and remodelling of membranes. To gain insight into the lipid remodelling mechanisms during autophagy, we have systematically investigated whether lipid flippases are required for this pathway in the yeast Saccharomyces cerevisiae. We found that the flippase Drs2, which transfers phosphatidylserine and phosphatidylethanolamine from the lumenal to the cytosolic leaflet of the limiting membrane at the trans-Golgi network, is required for normal progression of autophagy. We also show that Drs2 is important for the trafficking of the core Atg protein Atg9. Atg9 is a transmembrane protein important for autophagosome biogenesis and its anterograde transport from its post-Golgi reservoirs to the site of autophagosome formation is severely impaired in the absence of Drs2. Thus, our results identify a novel autophagy player and highlight that membrane asymmetry regulates early autophagy steps.

脂质翻转酶Drs2在自噬过程中调节Atg9的顺行转运
大自噬/自噬是一种保守的分解代谢途径,在此过程中,细胞物质被隔离在新形成的称为自噬体的双膜囊泡中,并被输送到真核细胞的裂解室进行降解。自噬体的生物发生依赖于核心的自噬相关(Atg)机制,并涉及膜的大量供应和重塑。为了深入了解自噬过程中的脂质重塑机制,我们系统地研究了酿酒酵母中该途径是否需要脂质翻转酶。我们发现翻转酶Drs2将磷脂酰丝氨酸和磷脂酰乙醇胺从内腔转移到反式高尔基体网络的限制膜的胞浆小叶,这是自噬正常进行所必需的。我们还表明Drs2对于核心Atg蛋白Atg9的运输是重要的。Atg9是一种对自噬某些生物发生很重要的跨膜蛋白,在缺乏Drs2的情况下,其从高尔基体后贮存器到自噬体形成位点的顺行转运严重受损。因此,我们的研究结果确定了一种新的自噬参与者,并强调了膜不对称调节早期自噬步骤
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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