摘要
自噬是真核细胞内一种高度保守的自我降解过程,通过清除受损细胞器、异常蛋白质及入侵的病原体来维持细胞内稳态,并在应激条件下为细胞提供能量和物质支持,实现细胞内物质的循环利用与更新。自噬相关蛋白(autophagy-related proteins,ATGs)是这一过程的核心执行者。ATG5作为自噬过程中的核心蛋白,通过2个泛素样结构域(UblA和UblB)和1个富含螺旋的结构域与ATG12、ATG16L1等蛋白相互作用形成复合物,驱动自噬体的形成与延伸。在自噬过程中,ATG5通过促进LC3脂化介导自噬体膜延伸。ATG5的翻译后修饰(如磷酸化、泛素化和SUMO化)进一步精细调控其功能,影响自噬体的成熟和细胞定位。ATG5不仅参与自噬调控,还在细胞凋亡、炎症反应、DNA损伤修复及代谢调控等非自噬途径中发挥重要作用。此外,ATG5的异常表达或功能失调与肿瘤、神经退行性疾病、自身免疫性疾病和代谢性疾病等多种疾病密切相关。笔者系统综述了ATG5的结构特征、生物学功能及其在疾病中的作用机制,旨在为相关疾病的治疗提供借鉴和参考。
Autophagy is a highly conserved self-degradation process in eukaryotic cells that maintains intracellular homeostasis by removing damaged organelles,aberrant proteins,and invading pathogens.Under stress conditions,it provides cells with energy and material support,enabling the recycling and renewal of intracellular substances.Autophagy-related proteins(ATGs)are the core executors of this process.As a central protein in autophagy,ATG5 interacts with proteins such as ATG12 and ATG16L1 through two ubiquitin-like domains(UblA and UblB)and one helix-rich domain to form complexes,driving the formation and extension of autophagosomes.During autophagy,ATG5 mediates autophagosome membrane extension by promoting LC3 lipidation.Posttranslational modifications of ATG5(such as phosphorylation,ubiquitination and SUMOylation)further refine its function,affecting autophagosome maturation and cellular localization.ATG5 not only participates in autophagy regulation but also plays a crucial role in non-autophagic pathways such as apoptosis,inflammatory responses,DNA damage repair and metabolic regulation.Additionally,abnormal expression or dysfunction of ATG5 is closely associated with various diseases,including tumors,neurodegenerative diseases,autoimmune diseases and metabolic disorders.This article provides a systematic review of the structural characteristics,biological functions,and disease-related mechanisms of A TG5,aiming to offer insights and references for the treatment of related diseases.
作者
赵庆露
王炫杰
张瑞
ZHAO Qinglu;WANG Xuanjie;ZHANG Rui(Key Laboratory of Animal Medicine in Universities of Sichuan Province,Southwest Minzu University,Chengdu 610041,China)
出处
《中国畜牧兽医》
北大核心
2026年第2期598-609,共12页
China Animal Husbandry & Veterinary Medicine
基金
国家自然科学基金项目(32302870)
四川省青年基金项目(2025ZNSFSC1071)
西南民族大学引进人才科研启动金资助项目(RQD2023034)。
关键词
自噬
ATG5
结构特征
生物学功能
autophagy
A TG5
structural characterization
biological function
