Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Germany.
CIBSS - Centre for Integrative Biological Signalling Studies, University of Freiburg, Germany.
FEBS Lett. 2024 Jan;598(1):73-83. doi: 10.1002/1873-3468.14720. Epub 2023 Aug 23.
Macroautophagy, hereafter referred to as autophagy, is a complex process in which multiple membrane-remodeling events lead to the formation of a cisterna known as the phagophore, which then expands and closes into a double-membrane vesicle termed the autophagosome. During the past decade, enormous progress has been made in understanding the molecular function of the autophagy-related proteins and their role in generating these phagophores. In this Review, we discuss the current understanding of three membrane remodeling steps in autophagy that remain to be largely characterized; namely, the closure of phagophores, the maturation of the resulting autophagosomes into fusion-competent vesicles, and their fusion with vacuoles/lysosomes. Our review will mainly focus on the yeast Saccharomyces cerevisiae, which has been the leading model system for the study of molecular events in autophagy and has led to the discovery of the major mechanistic concepts, which have been found to be mostly conserved in higher eukaryotes.
自噬作用,以下简称自噬,是一个复杂的过程,其中多个膜重塑事件导致了被称为吞噬体的质膜内陷的形成,然后该质膜内陷进一步延伸和闭合形成双层膜囊泡,即自噬体。在过去的十年中,人们在理解自噬相关蛋白的分子功能及其在产生这些吞噬体中的作用方面取得了巨大进展。在这篇综述中,我们讨论了自噬中仍然在很大程度上有待阐明的三个膜重塑步骤的当前理解;即,吞噬体的闭合、由此产生的自噬体的成熟为融合有活性的囊泡,以及它们与液泡/溶酶体的融合。我们的综述将主要集中在酵母酿酒酵母上,它一直是自噬中分子事件研究的领先模式系统,并导致了主要的机制概念的发现,这些概念在高等真核生物中大多是保守的。