Lai Lunmeng, Tan Menglei, Hu Mingming, Yue Xiyue, Tao Lulu, Zhai Yanru, Li Yunsen
Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Mol Cell Biochem. 2025 Feb;480(2):639-658. doi: 10.1007/s11010-024-05009-w. Epub 2024 Apr 26.
Ferroptosis is a type of cell death that is caused by the oxidation of lipids and is dependent on the presence of iron. It was first characterized by Brent R. Stockwell in 2012, and since then, research in the field of ferroptosis has rapidly expanded. The process of ferroptosis-induced cell death is genetically, biochemically, and morphologically distinct from other forms of cellular death, such as apoptosis, necroptosis, and non-programmed cell death. Extensive research has been devoted to comprehending the intricate process of ferroptosis and the various factors that contribute to it. While the majority of these studies have focused on examining the effects of lipid metabolism and mitochondria on ferroptosis, recent findings have highlighted the significant involvement of signaling pathways and associated proteins, including Nrf2, P53, and YAP/TAZ, in this process. This review provides a concise summary of the crucial signaling pathways associated with ferroptosis based on relevant studies. It also elaborates on the drugs that have been employed in recent years to treat ferroptosis-related diseases by targeting the relevant signaling pathways. The established and potential therapeutic targets for ferroptosis-related diseases, such as cancer and ischemic heart disease, are systematically addressed.
铁死亡是一种由脂质氧化引起且依赖铁存在的细胞死亡类型。它于2012年首次由布伦特·R·斯托克韦尔进行描述,从那时起,铁死亡领域的研究迅速扩展。铁死亡诱导的细胞死亡过程在基因、生化和形态上与其他形式的细胞死亡不同,如凋亡、坏死性凋亡和非程序性细胞死亡。大量研究致力于理解铁死亡的复杂过程以及促成该过程的各种因素。虽然这些研究大多集中于考察脂质代谢和线粒体对铁死亡的影响,但最近的研究结果突出了信号通路及相关蛋白(包括Nrf2、P53和YAP/TAZ)在这一过程中的重要作用。本综述基于相关研究对与铁死亡相关的关键信号通路进行了简要总结。它还阐述了近年来通过靶向相关信号通路用于治疗铁死亡相关疾病的药物。系统地探讨了铁死亡相关疾病(如癌症和缺血性心脏病)已确定的和潜在的治疗靶点。