Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan 430068, China.
National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China.
Cells. 2023 Apr 11;12(8):1132. doi: 10.3390/cells12081132.
Autophagy is a highly conserved recycling process of eukaryotic cells that degrades protein aggregates or damaged organelles with the participation of autophagy-related proteins. Membrane bending is a key step in autophagosome membrane formation and nucleation. A variety of autophagy-related proteins (ATGs) are needed to sense and generate membrane curvature, which then complete the membrane remodeling process. The Atg1 complex, Atg2-Atg18 complex, Vps34 complex, Atg12-Atg5 conjugation system, Atg8-phosphatidylethanolamine conjugation system, and transmembrane protein Atg9 promote the production of autophagosomal membranes directly or indirectly through their specific structures to alter membrane curvature. There are three common mechanisms to explain the change in membrane curvature. For example, the BAR domain of Bif-1 senses and tethers Atg9 vesicles to change the membrane curvature of the isolation membrane (IM), and the Atg9 vesicles are reported as a source of the IM in the autophagy process. The amphiphilic helix of Bif-1 inserts directly into the phospholipid bilayer, causing membrane asymmetry, and thus changing the membrane curvature of the IM. Atg2 forms a pathway for lipid transport from the endoplasmic reticulum to the IM, and this pathway also contributes to the formation of the IM. In this review, we introduce the phenomena and causes of membrane curvature changes in the process of macroautophagy, and the mechanisms of ATGs in membrane curvature and autophagosome membrane formation.
自噬是真核细胞中一种高度保守的回收过程，在自噬相关蛋白的参与下降解蛋白质聚集体或受损的细胞器。膜弯曲是自噬体膜形成和成核的关键步骤。需要多种自噬相关蛋白 (ATG) 来感应和产生膜曲率，然后完成膜重塑过程。Atg1 复合物、Atg2-Atg18 复合物、Vps34 复合物、Atg12-Atg5 缀合系统、Atg8-磷脂酰乙醇胺缀合系统和跨膜蛋白 Atg9 通过其特定结构直接或间接地促进自噬体膜的产生，从而改变膜曲率。有三种常见的机制可以解释膜曲率的变化。例如，Bif-1 的 BAR 结构域感应并将 Atg9 囊泡固定到隔离膜 (IM) 上，改变 IM 的膜曲率，据报道，在自噬过程中，Atg9 囊泡是 IM 的来源。Bif-1 的两亲性螺旋直接插入磷脂双分子层，导致膜不对称性，从而改变 IM 的膜曲率。Atg2 形成了从内质网到 IM 的脂质运输途径，该途径也有助于 IM 的形成。在这篇综述中，我们介绍了巨自噬过程中膜曲率变化的现象和原因，以及 ATG 在膜曲率和自噬体膜形成中的机制。
