Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM.
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM.
J Cell Biol. 2022 Jul 4;221(7). doi: 10.1083/jcb.202203083. Epub 2022 Jun 14.
The process of membrane atg8ylation, defined herein as the conjugation of the ATG8 family of ubiquitin-like proteins to membrane lipids, is beginning to be appreciated in its broader manifestations, mechanisms, and functions. Classically, membrane atg8ylation with LC3B, one of six mammalian ATG8 family proteins, has been viewed as the hallmark of canonical autophagy, entailing the formation of characteristic double membranes in the cytoplasm. However, ATG8s are now well described as being conjugated to single membranes and, most recently, proteins. Here we propose that the atg8ylation is coopted by multiple downstream processes, one of which is canonical autophagy. We elaborate on these biological outputs, which impact metabolism, quality control, and immunity, emphasizing the context of inflammation and immunological effects. In conclusion, we propose that atg8ylation is a modification akin to ubiquitylation, and that it is utilized by different systems participating in membrane stress responses and membrane remodeling activities encompassing autophagy and beyond.
膜 ATG8 修饰过程，在此定义为 ATG8 家族泛素样蛋白与膜脂的缀合，其在更广泛的表现形式、机制和功能方面开始得到认识。经典地，LC3B 等 6 种哺乳动物 ATG8 家族蛋白的膜 ATG8 修饰被视为经典自噬的标志，涉及细胞质中特征性双层膜的形成。然而，ATG8 现在被很好地描述为与单层膜和最近的蛋白质结合。在这里，我们提出 ATG8 修饰被多种下游过程所采用，其中之一是经典自噬。我们详细阐述了这些对代谢、质量控制和免疫有影响的生物学结果，强调了炎症和免疫学效应的背景。总之，我们提出 ATG8 修饰类似于泛素化修饰，它被参与膜应激反应和膜重塑活动的不同系统利用，包括自噬和其他方面。
