Super-assembly of ER-phagy receptor Atg40 induces local ER remodeling at contacts with forming autophagosomal membranes
Super-assembly of ER-phagy receptor Atg40 induces local ER remodeling at contacts with forming autophagosomal membranes
复制标题
DOI：
10.1038/s41467-020-17163-y
复制
发表时间：
2020-07-03
影响因子：
16.6
通讯作者：
Nakatogawa, Hitoshi
中科院分区：
文献类型：
--
作者：
Mochida, Keisuke;Yamasaki, Akinori;Nakatogawa, Hitoshi
内质网（ER）通过称为ER-吞噬受体的蛋白质被自噬（ER-吞噬）选择性降解。在酿酒酵母中，Atg 40作为ER-吞噬受体，通过结合Atg 8形成自噬体膜来将ER片段隔离到自噬体中。在ER-吞噬过程中，部分ER在形态上重排，片段化，并加载到自噬体中，但其机制仍然知之甚少。在这里，我们发现，Atg 40分子组装在ER膜的同时，通过与Atg 8的多价相互作用形成自噬体。Atg 8介导的Atg 40的超组装产生高度弯曲的ER区域，这取决于其网状结构域，并支持将这些区域包装成自噬体。此外，Atg 40与Atg 8的紧密结合是通过Atg 8家族相互作用基序的短螺旋C-末端实现的，并且在哺乳动物ER-吞噬受体中也观察到该特征。因此，这项研究大大推进了我们对ER-吞噬机制的理解，也为其他细胞器的选择性自噬中的细胞器片段化提供了见解。ER经历自噬（ER-吞噬）以进行周转，Atg 40充当受体以在自噬体中与Atg 8隔离ER。在这里，作者表明Atg 40通过与Atg 8相互作用而聚集，以产生局部膜曲率并促进自噬体包装。
The endoplasmic reticulum (ER) is selectively degraded by autophagy (ER-phagy) through proteins called ER-phagy receptors. In Saccharomyces cerevisiae, Atg40 acts as an ER-phagy receptor to sequester ER fragments into autophagosomes by binding Atg8 on forming autophagosomal membranes. During ER-phagy, parts of the ER are morphologically rearranged, fragmented, and loaded into autophagosomes, but the mechanism remains poorly understood. Here we find that Atg40 molecules assemble in the ER membrane concurrently with autophagosome formation via multivalent interaction with Atg8. Atg8-mediated super-assembly of Atg40 generates highly-curved ER regions, depending on its reticulon-like domain, and supports packing of these regions into autophagosomes. Moreover, tight binding of Atg40 to Atg8 is achieved by a short helix C-terminal to the Atg8-family interacting motif, and this feature is also observed for mammalian ER-phagy receptors. Thus, this study significantly advances our understanding of the mechanisms of ER-phagy and also provides insights into organelle fragmentation in selective autophagy of other organelles. The ER is subject to autophagy (ER-phagy) for turnover, with Atg40 acting as a receptor to sequester ER with Atg8 in autophagosomes. Here, the authors show that Atg40 is clustered by interaction with Atg8 to generate local membrane curvature and promote autophagosome packing.