Department of Oral and Maxillofacial Reconstruction, The Affiliated Hospital of Qingdao University, Qingdao 266555, China; School of Stomatology, Qingdao University, Qingdao 266003, China; Key Lab of Oral Clinical Medicine, The Affiliated Hospital of Qingdao University, Qingdao 266003, China.
Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, China.
Biomed Pharmacother. 2023 Dec 31;169:115892. doi: 10.1016/j.biopha.2023.115892. Epub 2023 Nov 15.
Ferroptosis is an iron-dependent regulated cell death, mainly manifested by the production of reactive oxygen species and accumulation of lipid peroxides. It is distinct from other forms of cell death with regard to morphology and biochemistry, particularly in disrupting mitochondrial function. Mitochondria are essential compartments where the organism generates energy and are closely associated with the fate of ferroptosis. Currently, researchers focus on the potential value of ferroptosis and mitochondria for overcoming drug sensitivity and assisting in cancer therapy. In this review, we summarize the main mechanisms of ferroptosis (the GPX4-realated pathway, FSP1-related pathway, and iron metabolism pathway) and the functions and regulating pathways of mitochondria (the TCA cycle, oxidative phosphorylation, mitochondrial regulation of iron ions, and mtDNA) in ferroptosis. We believe that exploring the role of mitochondria in ferroptosis will help us understand the potential regulatory mechanisms of ferroptosis in cancer and help us find new therapeutic targets.
铁死亡是一种铁依赖性的调节性细胞死亡，主要表现为活性氧的产生和脂质过氧化物的积累。它在形态学和生物化学上与其他形式的细胞死亡不同，特别是在破坏线粒体功能方面。线粒体是生物体产生能量的重要隔室，与铁死亡的命运密切相关。目前，研究人员专注于铁死亡和线粒体在克服药物敏感性和辅助癌症治疗方面的潜在价值。在这篇综述中，我们总结了铁死亡的主要机制（GPX4 相关途径、FSP1 相关途径和铁代谢途径）以及线粒体的功能和调节途径（三羧酸循环、氧化磷酸化、线粒体对铁离子的调节和 mtDNA）在铁死亡中的作用。我们相信，探索线粒体在铁死亡中的作用将有助于我们理解铁死亡在癌症中的潜在调节机制，并帮助我们找到新的治疗靶点。
