Life Sciences Institute and Department of Molecular, University of Michigan, Ann Arbor, MI 48109-2216, USA.
J Cell Sci. 2011 Jan 15;124(Pt 2):161-70. doi: 10.1242/jcs.064576.
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.
自噬是一种细胞内溶酶体（空泡）降解过程，其特征是形成双层膜囊泡，称为自噬体，自噬体可以隔离细胞质。由于自噬参与细胞生长、存活、发育和死亡，因此必须适当调节自噬水平，事实上，自噬失调与许多人类病理生理学有关，如癌症、肌肉疾病、神经退行性疾病、心脏和肝脏疾病以及胃肠道疾病。最近在理解自噬机制的分子机制和自噬的调节方面取得了重大进展。然而，仍有许多悬而未决的问题，例如 Atg1 复合物如何被激活以及 PtdIns3K 的功能如何被调节，泛素样连接系统如何参与自噬以及噬菌斑扩张和自噬体形成的机制，TOR 信号通路调控自噬的网络如何被控制，以及自噬对细胞生存和细胞死亡的促进作用的潜在机制是什么。由于最近的几篇综述全面总结了自噬调控的最新进展，我们在本评论中重点关注该领域的主要未解决问题。
