摘要
铁死亡是铁依赖性的脂质过氧化作用驱动的一种独特的细胞死亡方式。与细胞凋亡、自噬性程序性细胞死亡和细胞焦亡等细胞死亡方式不同,铁死亡的主要特征是线粒体形态的改变,包括线粒体膜变得致密并伴随体积变小,以及外膜破裂和线粒体嵴的减少或消失。线粒体作为细胞代谢的核心,是铁代谢、脂质代谢和能量代谢中的重要细胞器。但是,线粒体如何参与铁死亡并在其进程中发挥怎样的作用仍存在争议。本文综述了现有对铁死亡发生和防御机制的认识,并且对线粒体在铁死亡进程中的促进和抑制作用进行了描述和分析,包括线粒体三羧酸循环和糖酵解、线粒体活性氧、线粒体脂质代谢对铁死亡的积极驱动过程,以及通过线粒体铁蛋白、线粒体二氢乳酸脱氢酶等分子对线粒体脂质过氧化物解毒并抑制铁死亡的作用机制。最后补充说明了其他涉及铁死亡的线粒体分子调控机制。本文通过综述线粒体在铁死亡进程中的最新研究进展,旨在对深入了解铁死亡中线粒体的功能及其对铁死亡发生发展的作用机制,为细胞生物学基础研究及临床相关疾病的研究提供理论依据和参考。
Ferroptosis is a unique mode of iron-dependent cell death driven by lipid peroxidation.It is characterized by morphological changes in mitochondria,including densification of mitochondrial membranes and associated reduction in the volume,rupture of outer membranes and reduction or disappearance of the mitochondrial crest,which is different from that of apoptosis,autophagy and pyroptosis.Mitochondria,as the core of cell metabolism,are important organelles for iron metabolism,lipid metabolism and energy metabolism.However,it remains controversial debates as how mitochondria participate in ferroptosis and the underlying mechanisms during its progression.This review summaries the current understanding of the occurrence and defense mechanisms of ferroptosis,and the role of mitochondria in promoting and inhibiting ferroptosis,which includes the tricarboxylic acid cycle and glycolysis,reactive oxygen species,and lipid metabolism in mitochondria and their roles in driving ferroptosis.Moreover,we also summarize the defense mechanisms against ferroptosis through detoxification of mitochondrial lipid peroxidation by mitochondrial dihydroorotate dehydrogenase,as well as mitochondrial ferritin.Other mitochondrial molecules and their regulation of ferroptosis is stated at the end.This paper reviews the latest research progress of mitochondria in the process of ferroptosis,which aims to further understand the function of mitochondria in ferroptosis and its mechanism in the occurrence and development of ferroptosis,and therefore provides a theoretical foundation for the basic research of cell biology and strategies for investigation of clinical diseases.
作者
刘磊
贾少晗
于鹏
LIU Lei;JIA Shao-Han;YU Peng(Key Laboratory of Molecular and Cellular Biology,Ministry of Education,Hebei Key Laboratory of Animal Physiology,Biochemistry and Molecular Biology,Laboratory of Molecular Iron Metabolism,College of Life Sciences,Hebei Normal University,Shijiazhuang 050024,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2023年第6期769-777,共9页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金项目(No.31970905)
河北省自然科学基金项目(No.2021205033)资助。
关键词
铁死亡
能量代谢
脂质过氧化
二氢乳酸脱氢酶
还原型辅酶Q
ferroptosis
energy metabolism
lipid peroxidation
dihydroorotate dehydrogenase
hydroquinone form of coenzyme Q
