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Mechanisms governing autophagosome biogenesis.
Nature Reviews Molecular Cell Biology ( IF 112.7 ) Pub Date : 2020-05-05 , DOI: 10.1038/s41580-020-0241-0
Hitoshi Nakatogawa 1
Affiliation  

Autophagosomes are double-membrane vesicles newly formed during autophagy to engulf a wide range of intracellular material and transport this autophagic cargo to lysosomes (or vacuoles in yeasts and plants) for subsequent degradation. Autophagosome biogenesis responds to a plethora of signals and involves unique and dynamic membrane processes. Autophagy is an important cellular mechanism allowing the cell to meet various demands, and its disruption compromises homeostasis and leads to various diseases, including metabolic disorders, neurodegeneration and cancer. Thus, not surprisingly, the elucidation of the molecular mechanisms governing autophagosome biogenesis has attracted considerable interest. Key molecules and organelles involved in autophagosome biogenesis, including autophagy-related (ATG) proteins and the endoplasmic reticulum, have been discovered, and their roles and relationships have been investigated intensely. However, several fundamental questions, such as what supplies membranes/lipids to build the autophagosome and how the membrane nucleates, expands, bends into a spherical shape and finally closes, have proven difficult to address. Nonetheless, owing to recent studies with new approaches and technologies, we have begun to unveil the mechanisms underlying these processes on a molecular level. We now know that autophagosome biogenesis is a highly complex process, in which multiple proteins and lipids from various membrane sources, supported by the formation of membrane contact sites, cooperate with biophysical phenomena, including membrane shaping and liquid-liquid phase separation, to ensure seamless segregation of the autophagic cargo. Together, these studies pave the way to obtaining a holistic view of autophagosome biogenesis.

中文翻译:

控制自噬生物发生的机制。

自噬体是在自噬过程中新形成的双膜囊泡,其吞噬范围广泛的细胞内物质,并将这种自噬货物转运至溶酶体(或酵母和植物中的液泡)以进行后续降解。自噬体生物发生对大量信号作出反应,并涉及独特而动态的膜过程。自噬是一种重要的细胞机制,可使细胞满足各种需求,其破坏会破坏体内稳态,并导致多种疾病,包括代谢紊乱,神经变性和癌症。因此,毫不奇怪,阐明控制自噬生物发生的分子机制引起了相当大的兴趣。涉及自噬生物发生的关键分子和细胞器,包括自噬相关(ATG)蛋白和内质网,已发现它们,并且对其作用和关系进行了深入研究。但是,已证明很难解决几个基本问​​题,例如什么提供膜/脂质来构建自噬体,以及膜如何成核,膨胀,弯曲成球形并最终闭合。尽管如此,由于最近对新方法和新技术的研究,我们已开始在分子水平上揭示这些过程的基础机理。我们现在知道自噬生物发生是一个高度复杂的过程,其中来自各种膜源的多种蛋白质和脂质在膜接触位点形成的支持下与生物物理现象(包括膜成形和液-液相分离)协同作用,以确保无缝自噬货物的隔离。一起,
更新日期:2020-05-05
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