Focus on ferroptosis regulation: Exploring novel mechanisms and applications of ferroptosis regulator.

Tian-Liang Ma, Jing-Xian Chen, Peng Zhu, Chao-Bin Zhang, Yong Zhou, Jia-Xi Duan

Journal: Life sciences 2022;307():120868

PMID: 35940216

Full Text on Elsevier Science View on PubMed

Abstract

Ferroptosis is a kind of iron-dependent regulatory necrosis characterized by the fatal accumulation of iron-dependent 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.

Address: Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan Engineering Research Center of Biomedical Metal and Ceramic Impants, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.; Department of Physiology, School of Basic Medical Science, Central South University, Changsha, Hunan 410078, China.; Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China. Electronic address: [email protected].

DOI: 10.1016/j.lfs.2022.120868

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MeSH Terms: Ferroptosis, Iron, Lipid Peroxidation, Lipid Peroxides, Oxidative Stress