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.

铁死亡是一种由铁依赖性脂质过氧化诱导的受调节细胞死亡形式，自 2012 年发现以来已得到广泛研究。铁死亡是由铁超载和 ROS 积累诱导的，受到各种细胞代谢和信号通路的调节。GSH-GPX4 途径、FSP1-CoQ10 途径、GCH1-BH4 途径、DHODH-CoQH2 系统和性激素可抑制铁死亡。线粒体铁代谢调节铁死亡，线粒体在铁死亡过程中也会发生形态变化，这些变化包括膜密度增加和线粒体嵴减少。此外，铁死亡期间线粒体能量代谢发生变化，氧化磷酸化和 ATP 生成速率增加导致糖酵解速率降低。此外，过度的氧化应激还会对线粒体造成不可逆的损伤，从而降低细胞器的完整性。ROS 的产生、线粒体膜电位、线粒体融合和裂变以及线粒体自噬也在铁死亡中发挥作用。值得注意的是，一些铁死亡抑制剂以线粒体为目标。铁死亡是与癌症进展相关的细胞死亡的主要机制。易转移或转移性癌细胞更容易发生铁死亡。诱导肿瘤细胞铁死亡显示出治疗耐药癌症的巨大潜力。在这篇综述中，我们对铁死亡的发现和特征进行了简要回顾，然后讨论了铁死亡的调控，并强调了线粒体在癌细胞铁死亡中所发挥的独特作用。此外，我们解释了铁死亡如何作为一把双刃剑发挥作用，以及旨在选择性操纵细胞死亡以根除癌症的新疗法。