摘要
铁死亡是2012年被发现的一种新的受调控的细胞死亡方式,其特征是铁依赖的脂质过氧化物的过度积累(可引起细胞死亡的水平).铁代谢、脂代谢、氨基酸代谢等多种调节机制参与了铁死亡的调控.内质网是蛋白质合成、加工、修饰、转运的重要细胞器.应激状态下,未折叠、错误折叠蛋白在内质网内过度积累,即可诱发内质网应激反应.内质网应激是细胞应对外界压力的保护性机制,但持续的、恶劣的应激也能引起细胞死亡.近年来的研究表明,铁死亡与内质网应激密切相关.在癌细胞中,铁死亡诱导剂能同步激活内质网应激反应,内质网应激通路的启动则抑制铁死亡,导致癌细胞产生抗药性.在某些病理情况下,内质网应激通路的激活却加剧了铁死亡的发生.铁死亡和内质网应激之间究竟存在怎样的密切联系,成为目前认识细胞死亡命运的重要科学问题.本文综述了铁死亡的调控通路以及铁死亡与内质网应激相互联系的最新进展,以期为铁死亡相关疾病的发生机制和治疗提供重要的新参考.
Ferroptosis is a newly identified form of regulated cell death(RCD)in 2012,which is characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels.The initiation of ferroptosis is tightly linked with numerous essential biological processes,including iron,lipid,amino acid dysregulation.The endoplasmic reticulum(ER)is a dynamic intracellular organelle,which plays an essential role in synthesis,folding,modification and transport of proteins.Under stress conditions,increased levels of unfolded or misfolded proteins within the ER lumen trigger a condition referred to as“ER stress”.The initial ER stress can protect cell for its survival,but prolonged or severe stress can lead to cell death.Recent studies reveal that ER stress is closely related to the process of ferroptosis.In cancer cells,the ferroptotic agents can induce ER stress and subsequently the ER stress pathways negatively regulate the activation of ferroptosis and result in drug resistance.However,under pathological process,ER stress promotes the activation of ferroptosis.The interconnections between ferroptosis and ER stress have become an important scientific topic in understanding the mechanisms of cell fate decision.This review summarized the regulatory networks of ferroptosis and the relationship between ferroptosis and ER stress.We expected to provide new insights and references for ferroptosis research and the therapeutic strategy of ferroptosis associated diseases.
作者
王培娜
刘远远
常彦忠
WANG PeiNa;LIU YuanYuan;CHANG YanZhong(The Laboratory of Iron Metabolism,College of Life Science,Hebei Normal University,Shijiazhuang 050024,China)
出处
《中国科学：生命科学》
CSCD
北大核心
2021年第2期126-134,共9页
Scientia Sinica(Vitae)
基金
国家自然科学基金(批准号:31520103908)资助。
关键词
铁
铁死亡
内质网应激
脂质过氧化
iron
ferroptosis
endoplasmic reticulum stress
lipid peroxidation
