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.

中文翻译：

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膜 atg8ylation 和自噬指南以及对免疫的思考

膜 atg8 化过程在本文中定义为泛素样蛋白 ATG8 家族与膜脂质的缀合，其更广泛的表现、机制和功能开始受到重视。传统上，LC3B（六种哺乳动物 ATG8 家族蛋白之一）的膜 atg8 化被视为经典自噬的标志，需要在细胞质中形成特征性双膜。然而，ATG8 现在被充分描述为与单膜以及最近的蛋白质缀合。在这里，我们提出 atg8 化是由多个下游过程共同参与的，其中之一是典型的自噬。我们详细阐述了这些影响新陈代谢、质量控制和免疫的生物输出，强调炎症和免疫效应的背景。总之，我们提出 atg8 化是一种类似于泛素化的修饰，并且它被参与膜应激反应和膜重塑活动（包括自噬等）的不同系统所利用。