Molecular regulation of autophagy machinery by mTOR‐dependent and ‐independent pathways,Annals of the New York Academy of Sciences

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Molecular regulation of autophagy machinery by mTOR‐dependent and ‐independent pathways
Annals of the New York Academy of Sciences ( IF 4.1 ) Pub Date : 2020-01-27 , DOI: 10.1111/nyas.14305
Md Abdul Alim Al-Bari ₁ , Pingyong Xu _{2,

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Affiliation

Macroautophagy is a lysosomal degradative pathway or recycling process that maintains cellular homeostasis. This autophagy involves a series of sequential processing events, such as initiation; elongation and nucleation of the isolation membrane; cargo recruitment and maturation of the autophagosome (AP); transport of the AP; docking and fusion of the AP with a late endosome or lysosome; and regeneration of the lysosome by the autophagic lysosomal reformation cycle. These events are critically coordinated by the action of a set of several key components, including autophagy‐related proteins (Atg), and regulated by intricate networks, such as mechanistic target of rapamycin (mTOR), a master regulator of autophagy, as well as mTOR‐independent signaling pathways. Among mTOR‐independent pathways, the transient receptor potential (TRP) calcium ion channel TRPML (mucolipin) subfamily is emerging as an important signaling channel to modulate lysosomal biogenesis and autophagy. This review discusses the recent advances in elucidating the molecular mechanisms and regulation of the autophagy process. Understanding these mechanisms may ultimately allow scientists and clinicians to control this process in order to improve human health.

中文翻译：

mTOR依赖性和非依赖性通路对自噬机制的分子调控

巨自噬是维持细胞稳态的溶酶体降解途径或再循环过程。这种自噬涉及一系列顺序处理事件，例如启动；隔离膜的伸长和成核；自噬体 (AP) 的货物招募和成熟；AP的运输；AP与晚期内体或溶酶体的对接和融合；和通过自噬溶酶体重组循环再生溶酶体。这些事件由一组几个关键成分的作用密切协调，包括自噬相关蛋白 (Atg)，并受复杂网络调节，如雷帕霉素的机械靶标 (mTOR)，自噬的主要调节剂，以及mTOR 独立的信号通路。在 mTOR 独立通路中，瞬时受体电位 (TRP) 钙离子通道 TRPML (粘蛋白) 亚家族正在成为调节溶酶体生物发生和自噬的重要信号通道。本综述讨论了阐明自噬过程的分子机制和调控的最新进展。了解这些机制可能最终使科学家和临床医生能够控制这一过程，以改善人类健康。

更新日期：2020-01-27

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