Department of Biochemistry, and Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
Bioessays. 2024 Jun;46(6):e2300243. doi: 10.1002/bies.202300243. Epub 2024 Apr 9.
The autophagy initiation complex is brought about via a highly ordered and stepwise assembly process. Two crucial signaling molecules, mTORC1 and AMPK, orchestrate this assembly by phosphorylating/dephosphorylating autophagy-related proteins. Activation of Atg1 followed by recruitment of both Atg9 vesicles and the PI3K complex I to the PAS (phagophore assembly site) are particularly crucial steps in its formation. Ypt1, a small Rab GTPase in yeast cells, also plays an essential role in the formation of the autophagy initiation complex through multiple regulatory pathways. In this review, our primary focus is to discuss how signaling molecules initiate the assembly of the autophagy initiation complex, and highlight the significant roles of Ypt1 in this process. We end by addressing issues that need future clarification.
自噬体起始复合物的形成是通过高度有序和逐步的组装过程实现的。两个关键的信号分子，mTORC1 和 AMPK，通过磷酸化/去磷酸化自噬相关蛋白来协调这个组装过程。Atg1 的激活，以及 Atg9 小泡和 PI3K 复合物 I 向 PAS（噬泡组装位点）的募集，是其形成的特别关键步骤。在酵母细胞中，Ypt1 是一种小的 Rab GTPase，它也通过多种调节途径在自噬体起始复合物的形成中发挥重要作用。在这篇综述中，我们的主要重点是讨论信号分子如何启动自噬体起始复合物的组装，并强调 Ypt1 在这个过程中的重要作用。最后我们讨论了需要未来澄清的问题。
