The regulation of autophagy - unanswered questions
The regulation of autophagy - unanswered questions
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DOI：
10.1242/jcs.064576
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发表时间：
2011-01-15
影响因子：
4
通讯作者：
Klionsky, Daniel J.
中科院分区：
文献类型：
--
作者：
Chen, Yongqiang;Klionsky, Daniel J.
自噬是一种细胞内溶酶体（空泡）降解过程，其特征在于形成双膜囊泡，称为自噬体，其隔离细胞质。由于自噬参与细胞生长、存活、发育和死亡，因此自噬的水平必须得到适当的调节，如失调的自噬与许多人类病理生理学有关的事实所示，例如癌症、肌病、神经变性、心脏和肝脏疾病以及胃肠道疾病。近年来，对自噬机制的分子机制和自噬的调控机制的研究取得了很大进展。然而，仍有许多未解之谜，如Atg1复合物如何被激活和PtdIns3K的功能如何被调节，泛素样缀合系统如何参与自噬以及吞噬细胞扩增和自噬体形成的机制，调节自噬的TOR信号通路网络如何被控制，以及自噬作用的促细胞存活和促细胞死亡的潜在机制。由于最近的几篇综述已经全面总结了自噬调控的最新进展，我们在这篇评论中集中讨论了该领域尚未解决的主要问题。
Autophagy is an intracellular lysosomal (vacuolar) degradation process that is characterized by the formation of double-membrane vesicles, known as autophagosomes, which sequester cytoplasm. As autophagy is involved in cell growth, survival, development and death, the levels of autophagy must be properly regulated, as indicated by the fact that dysregulated autophagy has been linked to many human pathophysiologies, such as cancer, myopathies, neurodegeneration, heart and liver diseases, and gastrointestinal disorders. Substantial progress has recently been made in understanding the molecular mechanisms of the autophagy machinery, and in the regulation of autophagy. However, many unanswered questions remain, such as how the Atg1 complex is activated and the function of PtdIns3K is regulated, how the ubiquitin-like conjugation systems participate in autophagy and the mechanisms of phagophore expansion and autophagosome formation, how the network of TOR signaling pathways regulating autophagy are controlled, and what the underlying mechanisms are for the pro-cell survival and the pro-cell death effects of autophagy. As several recent reviews have comprehensively summarized the recent progress in the regulation of autophagy, we focus in this Commentary on the main unresolved questions in this field.