DAMP Laboratory, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Guangzhou Medical University, Guangzhou, China.
Antioxid Redox Signal. 2023 Jul;39(1-3):79-101. doi: 10.1089/ars.2022.0202. Epub 2023 Mar 9.
Autophagy is a self-degrading process that determines cell fate in response to various environmental stresses. In contrast to autophagy-mediated cell survival, the signals, mechanisms, and effects of autophagy-dependent cell death remain obscure. The discovery of autophagy-dependent ferroptosis provides a paradigm for understanding the relationship between aberrant degradation pathways and excessive lipid peroxidation in driving regulated cell death. Ferroptosis was originally described as an autophagy-independent and iron-mediated nonapoptotic cell death. Current studies reveal that the level of intracellular autophagy is positively correlated with ferroptosis sensitivity. Selective autophagic degradation of proteins (, ferritin, SLC40A1, ARNTL, GPX4, and CDH2) or organelles (, lipid droplets or mitochondria) promotes ferroptosis by inducing iron overload and/or lipid peroxidation. Several upstream autophagosome regulators (, TMEM164), downstream autophagy receptors (, HPCAL1), or danger signals (, DCN) are selectively required for ferroptosis-related autophagy, but not for starvation-induced autophagy. The induction of autophagy-dependent ferroptosis is an effective approach to eliminate drug-resistant cancer cells. How different organelles selectively activate autophagy to modulate ferroptosis sensitivity is not fully understood. Identifying direct protein effectors of ferroptotic cell death remains a challenge. Further understanding of the molecular mechanics and immune consequences of autophagy-dependent ferroptosis is critical for the development of precision antitumor therapies. . 39, 79-101.
自噬是一种自我降解的过程，它可以根据各种环境压力来决定细胞的命运。与自噬介导的细胞存活不同，自噬依赖性细胞死亡的信号、机制和效应仍不清楚。自噬依赖性铁死亡的发现为理解异常降解途径与驱动细胞程序性死亡的过度脂质过氧化之间的关系提供了范例。铁死亡最初被描述为一种不依赖自噬和铁介导的非凋亡性细胞死亡。目前的研究表明，细胞内自噬水平与铁死亡敏感性呈正相关。选择性自噬性降解蛋白（如 ferritin、SLC40A1、ARNTL、GPX4 和 CDH2）或细胞器（如脂滴或线粒体）通过诱导铁过载和/或脂质过氧化来促进铁死亡。几个上游自噬体调节剂（如 TMEM164）、下游自噬受体（如 HPCAL1）或危险信号（如 DCN）是铁死亡相关自噬所必需的，但不是饥饿诱导的自噬所必需的。诱导自噬依赖性铁死亡是消除耐药癌细胞的有效方法。不同的细胞器如何选择性地激活自噬来调节铁死亡敏感性尚不完全清楚。鉴定铁死亡细胞的直接蛋白效应因子仍然是一个挑战。进一步了解自噬依赖性铁死亡的分子机制和免疫后果对于开发精确的抗肿瘤治疗方法至关重要。
