铁过氧化脂质死亡是一种由铁依赖的脂质过氧化引发的调控性细胞死亡形式，自2012年发现以来已经得到广泛研究。铁超负荷和ROS积累导致了铁过氧化脂质死亡的发生，并且其受到多种细胞代谢和信号通路的调节。谷胱甘肽-谷胱甘肽过氧化物酶4途径、FSP1-CoQ10途径、GCH1-BH4途径、DHODH-CoQH2系统以及性激素能够抑制铁过氧化脂质死亡。线粒体铁代谢调节了铁过氧化脂质死亡，且在铁过氧化脂质死亡中线粒体也发生了形态改变，其中包括膜密度增加和线粒体嵴（cristae）减少。此外，铁过氧化脂质死亡过程中线粒体能量代谢也发生了变化，氧化磷酸化和ATP生产速率的增加导致糖酵解速率降低。此外，过度的氧化应激会对线粒体造成不可逆损伤，降低细胞器完整性。ROS产生、线粒体膜电位、线粒体融合和分裂以及线粒体吞噬在铁过氧化脂质死亡中也起到重要作用。值得注意的是，一些铁过氧化脂质死亡抑制剂作用于线粒体。铁过氧化脂质死亡是与癌症进展相关的主要细胞死亡机制，易转移或转移性癌细胞对铁过氧化脂质死亡更为敏感。诱导肿瘤细胞发生铁过氧化脂质死亡在治疗耐药性癌症方面显示出极大的潜力。在本综述中，我们简要回顾了铁过氧化脂质死亡的发现和特点，然后讨论了对铁过氧化脂质死亡的调控，并着重介绍了线粒体在癌细胞铁过氧化脂质死亡中所起到的独特作用。此外，我们解释了铁过氧化脂质死亡是如何成为一把双刃剑以及针对选择性操纵细胞死亡以达到癌细胞根除的新疗法。© 2023. 作者（们）。

Ferroptosis is a form of regulated cell death induced by iron-dependent lipid peroxidation, and it has been studied extensively since its discovery in 2012. Induced by iron overload and ROS accumulation, ferroptosis is modulated by various cellular metabolic and signaling pathways. The GSH-GPX4 pathway, the FSP1-CoQ10 pathway, the GCH1-BH4 pathway, the DHODH-CoQH2 system and the sex hormones suppress ferroptosis. Mitochondrial iron metabolism regulates ferroptosis and mitochondria also undergo a morphological change during ferroptosis, these changes include increased membrane density and reduced mitochondrial cristae. Moreover, mitochondrial energy metabolism changes during ferroptosis, the increased oxidative phosphorylation and ATP production rates lead to a decrease in the glycolysis rate. In addition, excessive oxidative stress induces irreversible damage to mitochondria, diminishing organelle integrity. ROS production, mitochondrial membrane potential, mitochondrial fusion and fission, and mitophagy also function in ferroptosis. Notably, some ferroptosis inhibitors target mitochondria. Ferroptosis is a major mechanism for cell death associated with the progression of cancer. Metastasis-prone or metastatic cancer cells are more susceptible to ferroptosis. Inducing ferroptosis in tumor cells shows very promising potential for treating drug-resistant cancers. In this review, we present a brief retrospect of the discovery and the characteristics of ferroptosis, then we discuss the regulation of ferroptosis and highlight the unique role played by mitochondria in the ferroptosis of cancer cells. Furthermore, we explain how ferroptosis functions as a double-edged sword as well as novel therapies aimed at selectively manipulating cell death for cancer eradication.© 2023. The Author(s).