Kumar Suresh, Jia Jingyue, Deretic Vojo
Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Cell Stress. 2021 Aug 12;5(9):128-142. doi: 10.15698/cst2021.09.255. eCollection 2021 Sep.
The yeast Atg8 protein and its paralogs in mammals, mammalian Atg8s (mAtg8s), have been primarily appreciated for their participation in autophagy. However, lipidated mAtg8s, including the most frequently used autophagosomal membrane marker LC3B, are found on cellular membranes other than autophagosomes. Here we put forward a hypothesis that the lipidation of mAtg8s, termed 'Atg8ylation', is a general membrane stress and remodeling response analogous to the role that ubiquitylation plays in tagging proteins. Ubiquitin and mAtg8s are related in sequence and structure, and the lipidation of mAtg8s occurs on its C-terminal glycine, akin to the C-terminal glycine of ubiquitin. Conceptually, we propose that mAtg8s and Atg8ylation are to membranes what ubiquitin and ubiquitylation are to proteins, and that, like ubiquitylation, Atg8ylation has a multitude of downstream effector outputs, one of which is autophagy.
酵母自噬相关蛋白8（Atg8）及其在哺乳动物中的同源物——哺乳动物自噬相关蛋白8（mAtg8s），主要因其参与自噬过程而受到关注。然而，脂化的mAtg8s，包括最常用的自噬体膜标记物LC3B，在自噬体以外的细胞膜上也有发现。在此，我们提出一个假说，即mAtg8s的脂化作用，称为“Atg8化”，是一种类似于泛素化在标记蛋白质中所起作用的普遍的膜应激和重塑反应。泛素和mAtg8s在序列和结构上相关，mAtg8s的脂化作用发生在其C末端甘氨酸上，类似于泛素的C末端甘氨酸。从概念上讲，我们认为mAtg8s和Atg8化对于膜的作用就如同泛素和泛素化对于蛋白质的作用，并且，与泛素化一样，Atg8化有多种下游效应输出，其中之一就是自噬。
