细胞程序性死亡研究进展  

The mechanism insights into programmed cell death

作　　者：陈朝红(综述) 刘志红(审校) CHEN Zhaohong;LIU Zhihong(National Clinical Research Center for Kidney Diseases,Jinling Hospital,Nanjing 210016,China)

机构地区：[1]东部战区总医院国家肾脏疾病临床医学研究中心,南京210016

出　　处：《肾脏病与透析肾移植杂志》2025年第1期57-64,共8页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：国家自然科学基金面上项目(82070755)。

摘　　要：细胞程序性死亡是一种由特定分子机制调控的生物过程,在维持机体稳态和疾病发展中发挥重要作用。凋亡、坏死性凋亡和焦亡是细胞程序性死亡的不同形式。在这些过程中,胱天蛋白酶(caspase)发挥了关键的调节作用。当细胞遭遇外部刺激或内部压力时,caspase-3/7被上游的caspase-8/9激活,负责执行凋亡过程;如果caspase-8的功能受到抑制,受体相互作用蛋白激酶3(RIPK3)将被激活,进而磷酸化混合谱系激酶结构域样蛋白(MLKL),触发其寡聚和破膜活性,导致细胞发生凋亡性坏死。炎性caspase-1/4/5/11通过裂解Gasdermin家族分子诱导细胞焦亡。此外,膜磷脂的多不饱和脂肪酸的过氧化会引发铁死亡,这是一种非caspase依赖的坏死性死亡方式。本文概述了主要的细胞死亡机制及其最新研究进展,以及它们与疾病之间的关联。Programmed cell death is a biological process regulated by molecular mechanisms.Apoptosis,necroptosis,and pyroptosis are three modalities of programmed cell death.In these processes,caspases play a key regulatory role.Upon exposure to external stimuli or internal stressors,caspase-3/7 is activated by upstream caspase-8/9.This cascade orchestrates the execution of apoptosis.If caspase-8 is inhibited,it leads to the activation of receptor-interacting protein kinase 3(RIPK3),which in turn phosphorylates mixed lineage kinase domain-like protein(MLKL),triggering its oligomerization and subsequent membrane permeabilization,resulting in necroptosis.caspase-1/4/5/11 induce pyroptosis by cleaving Gasdermin family molecules.Furthermore,the oxidation of polyunsaturated fatty acids within membrane phospholipids can initiate ferroptosis,a distinct caspase-independent pathway of cell demise.This review summarizes the mechanisms underlying cell death,highlights recent research advancements,and discusses their implications for disease understanding.

关 键 词：程序性细胞死亡 半胱氨酸蛋白酶 凋亡 坏死性凋亡 焦亡 铁死亡 

分 类 号：R363[医药卫生—病理学]