Huang Xiangliang, Yan Hao, Xu Zhifei, Yang Bo, Luo Peihua, He Qiaojun
Center for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Cell Commun Signal. 2025 Mar 26;23(1):151. doi: 10.1186/s12964-025-02135-w.
Autophagy is a lysosome-dependent degradation pathway for recycling intracellular materials and removing damaged organelles, and it is usually considered a prosurvival process in response to stress stimuli. However, increasing evidence suggests that autophagy can also drive cell death in a context-dependent manner. The bulk degradation of cell contents and the accumulation of autophagosomes are recognized as the mechanisms of cell death induced by autophagy alone. However, autophagy can also drive other forms of regulated cell death (RCD) whose mechanisms are not related to excessive autophagic vacuolization. Notably, few reviews address studies on the transformation from autophagy to RCD, and the underlying molecular mechanisms are still vague.
This review aims to summarize the existing studies on autophagy-mediated RCD, to elucidate the mechanism by which autophagy initiates RCD, and to comprehensively understand the role of autophagy in determining cell fate.
This review highlights the prodeath effect of autophagy, which is distinct from the generally perceived cytoprotective role, and its mechanisms are mainly associated with the selective degradation of proteins or organelles essential for cell survival and the direct involvement of the autophagy machinery in cell death. Additionally, this review highlights the need for better manipulation of autophagy activation or inhibition in different pathological contexts, depending on clinical purpose.
自噬是一种依赖溶酶体的降解途径，用于回收细胞内物质和清除受损细胞器，通常被认为是一种应对应激刺激的促生存过程。然而，越来越多的证据表明，自噬也可以在特定环境下导致细胞死亡。细胞内容物的大量降解和自噬体的积累被认为是自噬单独诱导细胞死亡的机制。然而，自噬也可以驱动其他形式的程序性细胞死亡（RCD），其机制与过度的自噬空泡化无关。值得注意的是，很少有综述涉及自噬向RCD转变的研究，其潜在的分子机制仍然模糊不清。
本综述旨在总结关于自噬介导的RCD的现有研究，阐明自噬启动RCD的机制，并全面了解自噬在决定细胞命运中的作用。
本综述强调了自噬的促死亡作用，这与通常认为的细胞保护作用不同，其机制主要与细胞存活所必需的蛋白质或细胞器的选择性降解以及自噬机制直接参与细胞死亡有关。此外，本综述强调根据临床目的，在不同病理情况下更好地调控自噬激活或抑制的必要性。
