铁死亡途径及其相关分子泛素化修饰的研究进展

Research progress in ferroptosis pathways and ubiquitination modification of ferroptosis-related molecules

铁死亡是细胞膜上多不饱和脂肪酸磷脂过氧化损伤引起的一种铁依赖性细胞死亡方式,涉及多条途径,包括铁稳态调节途径、胱氨酸谷氨酸反向转运体(system X-C)途径和电压依赖性阴离子通道(voltage-dependent anion channel,VDAC)途径等。铁死亡参与多种疾病(如心梗、脑卒中、癌症和退行性疾病等)的发生发展过程。泛素化是机体内各种蛋白分子翻译后修饰的重要形式。研究表明,通过对铁死亡途径相关分子泛素化水平的调控可调节细胞铁死亡。靶向调控铁死亡途径相关分子泛素化水平可有效促进或抑制铁死亡,有望成为治疗癌症或心脑血管疾病的新策略。该文将就铁死亡途径及其相关分子泛素化修饰的研究进展作一综述。

Ferroptosis is an iron-dependent cell death caused by phospholipid peroxidation damage of polyunsaturated fatty acids on cell membranes and involves several pathways,including the iron homeostasis regulatory pathway,the cystine glutamate reverse transporter(system X-C)pathway and the voltage-dependent anion channel(VDAC)pathway.Ferroptosis is involved in the development of several diseases(e.g.myocardial infarction,stroke,cancer and degenerative diseases).The ubiquitination is an important post-translational modification of various protein molecules in the organism.Studies have shown that regulating the ubiquitination of ferroptosis pathway-related molecules can control cellular ferroptosis.Targeting the ubiquitination of ferroptosis pathway-related molecules can effectively promote or inhibit ferroptosis,which is expected to be a new strategy for the treatment of cancer or cardiovascular diseases.In this paper we review the progress of the ferroptosis pathways and the ubiquitination modification of ferroptosis-related molecules.