Department of Cellular Regulation, Division of Cellular and Molecular Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Int Immunol. 2009 Nov;21(11):1199-204. doi: 10.1093/intimm/dxp088. Epub 2009 Sep 7.
Autophagy is a catabolic process by which cells degrade their own cytoplasmic constituents. Cells respond to the stress response of nutrient deficiency by degrading a portion of their cellular components to produce amino acids and energy. Recently, it became evident that the autophagic machinery is also involved in a kind of innate immune system. Some bacteria that invade mammalian cells are eventually entrapped in an autophagic membrane structure. In this review, we describe the current understanding of three of the basic components of the canonical autophagy machinery-LC3, the Atg16L complex and phosphatidylinositol 3-phosphate (PI3P)-which are dynamically associated with the autophagic structure. LC3 is proposed to function in autophagosome closure, whereas the Atg16L complex functions as an E3-like protein in ubiquitination-like reactions in the LC3 lipidation system. PI3P is a key determinant of the autophagic membrane. Further, their relation to bactericidal autophagy (i.e. xenophagy) will be introduced.
自噬是一种细胞降解自身细胞质成分的分解代谢过程。当细胞感受到营养缺乏的应激反应时,会通过降解一部分细胞成分来产生氨基酸和能量。最近,人们发现自噬机制也参与了一种天然的免疫系统。一些入侵哺乳动物细胞的细菌最终会被包裹在自噬膜结构中。在这篇综述中,我们描述了目前对经典自噬机制的三个基本组成部分的理解——LC3、Atg16L 复合物和磷脂酰肌醇 3-磷酸(PI3P),它们与自噬结构动态相关。LC3 被认为在自噬体闭合中起作用,而 Atg16L 复合物在 LC3 脂质化系统的泛素样反应中作为一种 E3 样蛋白发挥作用。PI3P 是自噬膜的关键决定因素。此外,我们还将介绍它们与杀菌自噬(即异噬)的关系。