The mitochondrial regulation in ferroptosis signaling pathway and its potential strategies for cancer

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. [Display omitted] •Studies illuminated the main mechanisms of ferroptosis in cancer over the past few years.•Mitochondria play a vital role in the process of ferroptosis, the TCA cycle, the OXPHS pathway, mitochondrial regulation of iron ions, and mtDNA.•Targeting mitochondria-related function to influence ferroptosis associated pathways in cancer cells, and how these mechanisms can be an effective strategy for cancer therapy.