摘要
铁死亡是一种独特的、以铁依赖和脂质过氧化为特征的新型调节性细胞死亡形式。铁死亡在多个细胞器内均可发生,而线粒体依赖性铁死亡在诸如胃肠肿瘤等多种疾病演进中显得日益重要。线粒体作为细胞物质代谢和能量代谢的核心,通过位于其内膜的电子传递链等结构产生活性氧,从而引发线粒体依赖性铁死亡。同时,位于线粒体内膜外侧的二氢乳清酸脱氢酶等抗氧化系统抵抗铁死亡。通过靶向线粒体依赖性铁死亡相关靶点进行治疗,有望实现对胃肠肿瘤的精准诊治。本文综述了线粒体在铁死亡中的形态变化,并且对线粒体依赖性铁死亡的具体机制进行了详细总结,包括能量代谢、脂质代谢、铁代谢以及其他涉及的调控机制。同时,本文强调了线粒体依赖性铁死亡对胃肠肿瘤生物学的影响,以及其在胃肠肿瘤治疗上的潜在临床应用价值。本文拟通过深入探讨线粒体依赖性铁死亡的具体机制,以及其在胃肠肿瘤的预后预测和治疗中的潜在作用,旨在为胃肠肿瘤预后预测与治疗提供潜在的靶点。
Ferroptosis is a unique and novel form of regulated cell death characterized by iron dependence and lipid peroxidation.Ferroptosis can occur in multiple organelles,and more and more studies have found that mitochondria-dependent ferroptosis plays an important role in the progression of various diseases such as gastrointestinal tumors.Mitochondria,as the core of cellular substance and energy metabolism,can trigger mitochondria-dependent ferroptosis by producing reactive oxygen species through structures such as electron transport chains located in the inner membrane.It can also resist ferroptosis through antioxidant systems such as dihydroorotate dehydrogenase located on the outer side of the mitochondrial inner membrane.Therefore,by targeting the molecules related to mitochondria-dependent ferroptosis,it is expected to achieve accurate treatment of gastrointestinal tumors.This article reviews the morphological changes of mitochondria in ferroptosis,and summarizes the specific mechanisms of mitochondria-dependent ferroptosis,including energy metabolism,lipid metabolism,iron metabolism,and other regulatory mechanisms involved.At the same time,the effect of mitochondria-dependent ferroptosis on the biological studies of gastrointestinal tumors and its potential value in the treatment of gastrointestinal tumors were also illustrated.This article reviews the specific mechanism of mitochondria-dependent ferroptosis and its application in the prognostic prediction and treatment in gastrointestinal tumors,aiming to provide potential targets for the prognosis prediction and treatment of gastrointestinal tumors.
作者
吕忱聪
罗再
黄陈
LV Chen-Cong;LUO Zai;HUANG Chen(Department of Gastrointestinal Surgery,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2024年第12期1649-1658,共10页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金面上项目(No.82072662)
上海市青年科技英才扬帆计划(No.24YF2734700)资助。
关键词
线粒体
铁死亡
脂质过氧化
胃癌
结直肠癌
mitochondria
ferroptosis
lipid peroxidation
gastric cancer(GC)
colorectal cancer(CRC)
