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自噬体的生物发生和货物选择性。

Biogenesis and cargo selectivity of autophagosomes.

机构信息

Department of Biological Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel.

出版信息

Annu Rev Biochem. 2011;80:125-56. doi: 10.1146/annurev-biochem-052709-094552.

Abstract

Autophagy is a major catabolic pathway in eukaryotes, which is required for the lysosomal/vacuolar degradation of cytoplasmic proteins and organelles. Interest in the autophagy pathway has recently gained momentum largely owing to identification of multiple autophagy-related genes and recognition of its involvement in various physiological conditions. Here we review current knowledge of the molecular mechanisms regulating autophagy in mammals and yeast, specifically the biogenesis of autophagosomes and the selectivity of their cargo recruitment. We discuss the different steps of autophagy, from the signal transduction events that regulate it to the completion of this pathway by fusion with the lysosome/vacuole. We also review research on the origin of the autophagic membrane, the molecular mechanism of autophagosome formation, and the roles of two ubiquitin-like protein families and other structural elements that are essential for this process. Finally, we discuss the various modes of autophagy and highlight their functional relevance for selective degradation of specific cargos.

摘要

自噬是真核生物中的一种主要的分解代谢途径,对于溶酶体/液泡中细胞质蛋白和细胞器的降解是必需的。自噬途径的兴趣最近得到了增强,这主要是由于鉴定了多种自噬相关基因,并认识到它参与了各种生理条件。在这里,我们综述了哺乳动物和酵母中调节自噬的分子机制的最新知识,特别是自噬体的生物发生及其货物募集的选择性。我们讨论了自噬的不同步骤,从调节它的信号转导事件到通过与溶酶体/液泡融合完成这个途径。我们还综述了关于自噬膜起源、自噬体形成的分子机制以及两种泛素样蛋白家族和其他对这个过程至关重要的结构元件的研究。最后,我们讨论了各种自噬模式,并强调了它们在选择性降解特定货物方面的功能相关性。

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