Zhu Ye, Fujimaki Motoki, Rubinsztein David C
Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, The Keith Peters Building, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, UK; UK Dementia Research Institute, University of Cambridge, Cambridge Institute for Medical Research, The Keith Peters Building, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, UK.
Department of Neurology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan.
Trends Cell Biol. 2025 Mar 5. doi: 10.1016/j.tcb.2025.01.005.
Ferroptosis is an iron-dependent cell death pathway that, until recently, has been considered to be dependent on autophagy. However, recent studies have reported conflicting results, raising the question about which cell contexts determine the roles of autophagy in ferroptosis. This opinion article addresses this question by summarizing the contexts and/or diseases in which autophagy is a driver or suppressor of ferroptosis. The execution of ferroptosis depends on levels of (labile) iron, unsaturated (phospho)lipids and free radicals. We propose that the cell context in which these three factors and/or their upstream pathways are differentially regulated dictates whether autophagy positively or negatively regulates ferroptosis.
铁死亡是一种铁依赖性细胞死亡途径，直到最近，它一直被认为依赖于自噬。然而，最近的研究报告了相互矛盾的结果，这就提出了一个问题：在哪些细胞环境中自噬决定了其在铁死亡中的作用。这篇观点文章通过总结自噬作为铁死亡驱动因素或抑制因素的环境和/或疾病来探讨这个问题。铁死亡的发生取决于（不稳定）铁、不饱和（磷酸）脂质和自由基的水平。我们认为，这三种因素和/或其上游途径受到差异调节的细胞环境决定了自噬对铁死亡是正向还是负向调节。
