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Since its identification in 2012, extensive research has unveiled its involvement in the pathophysiology of numerous diseases, including cancers, neurodegenerative disorders, organ injuries, infectious diseases, autoimmune conditions, metabolic disorders, and skin diseases. Oxidizable lipids, overload iron, and compromised antioxidant systems are known as critical prerequisites for driving overwhelming lipid peroxidation, ultimately leading to plasma membrane rupture and ferroptotic cell death. However, the precise regulatory networks governing ferroptosis and ferroptosis\u2010targeted therapy in these diseases remain largely undefined, hindering the development of pharmacological agonists and antagonists. In this review, we first elucidate core mechanisms of ferroptosis and summarize its epigenetic modifications (e.g., histone modifications, DNA methylation, noncoding RNAs, and N6\u2010methyladenosine modification) and nonepigenetic modifications (e.g., genetic mutations, transcriptional regulation, and posttranslational modifications). We then discuss the association between ferroptosis and disease pathogenesis and explore therapeutic approaches for targeting ferroptosis. We also introduce potential clinical monitoring strategies for ferroptosis. Finally, we put forward several unresolved issues in which progress is needed to better understand ferroptosis. We hope this review will offer promise for the clinical application of ferroptosis\u2010targeted therapies in the context of human health and disease.<\/jats:p>","DOI":"10.1002\/mco2.70010","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T12:39:29Z","timestamp":1732106369000},"source":"Crossref","is-referenced-by-count":79,"title":["Ferroptosis: mechanisms and therapeutic targets"],"prefix":"10.1002","volume":"5","author":[{"given":"Qian","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Dermatology Xiangya Hospital Central South University  Changsha Hunan Province China"},{"name":"National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology  Changsha Hunan Province China"},{"name":"Furong Laboratory  Changsha Hunan Province China"},{"name":"Hunan Key Laboratory of Skin Cancer and Psoriasis Hunan Engineering Research Center of Skin Health and Disease Xiangya Hospital Central South University  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