Journal
LIFE SCIENCES
Volume 307, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2022.120868
Keywords
Ferroptosis; Lipid peroxidation; Iron metabolism; Mitochondria; Ferroptosis inducers; Ferroptosis inhibitors
Funding
- National Natural Science Foundation of China [91949110, 82170096]
- Open Project of the State Key Laboratory of Trauma, Burns, and Combined Injury, Army Medical University [SKLKF201702]
- National University Student Innovation Program [2020105330257]
- High School Innovation Fund of Hunan province [19K103]
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Ferroptosis is an iron-dependent regulatory necrosis characterized by the accumulation of iron-dependent lipid peroxides in the plasma membrane and subsequent oxidative damage. It is mainly related to iron toxicity, lipid peroxidation, and mitochondrial dysfunction. Understanding the specific mechanism of ferroptosis and exploring strategies for its regulation have significant clinical implications.
Ferroptosis is a kind of iron-dependent regulatory necrosis characterized by the fatal accumulation of irondependent lipid peroxides in the plasma membrane and the final oxidative damage of the cell membrane. Morphologically, ferroptosis features high membrane density, decreased or disappeared cristae, rupture of the mitochondrial outer membrane, plasma membrane integrity loss, cytoplasmic swelling, and organelle swelling. Under physiological conditions, ferroptosis occurs through two major pathways, the extrinsic or transporter-dependent pathway and the intrinsic or enzyme-regulated pathway, triggered by a series of small molecules inside and outside the cell. At present, it is assumed that ferroptosis is mainly related to abnormal toxicity of iron, lipid peroxidation, and mitochondrial dysfunction. With more detailed studies, ferroptosis plays potential pathogenic roles in multisystem diseases as a pathological response, and targeted regulation of ferroptosis in treating ferroptosis-related diseases has broad prospects. In conclusion, it is of great clinical significance to further clarify the specific mechanism of ferroptosis and explore new strategies for ferroptosis regulation. The present review emphatically summarizes the latest mechanism of ferroptosis, focusing on the regulation mechanism and clinical application of ferroptosis inducers and inhibitors. We are devoted to providing new ideas for the further study of ferroptosis and the diagnosis and treatment of ferroptosis-related multisystem diseases.
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