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.
Life Sci. 2022 Oct 15;307:120868. doi: 10.1016/j.lfs.2022.120868. Epub 2022 Aug 6.
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.
铁死亡是一种铁依赖性的调节性细胞坏死，其特征是细胞膜上铁依赖性脂质过氧化物的致命积累，最终导致细胞膜的氧化损伤。形态学上，铁死亡表现为膜密度高、嵴减少或消失、线粒体外膜破裂、质膜完整性丧失、细胞质肿胀和细胞器肿胀。在生理条件下，铁死亡通过细胞内外的两条主要途径，即外在的或依赖转运体的途径和内在的或酶调节的途径发生，由一系列细胞内外的小分子触发。目前，铁死亡主要与铁的异常毒性、脂质过氧化和线粒体功能障碍有关。随着更详细的研究，铁死亡作为一种病理反应，在多系统疾病中发挥潜在的致病作用，针对铁死亡的靶向调节在治疗铁死亡相关疾病方面具有广阔的前景。总之，进一步阐明铁死亡的具体机制并探索铁死亡调节的新策略具有重要的临床意义。本综述着重总结了铁死亡的最新机制，重点阐述了铁死亡诱导剂和抑制剂的调节机制及其在临床中的应用。我们致力于为铁死亡和铁死亡相关多系统疾病的诊断和治疗的进一步研究提供新的思路。
