内质网应激诱导内质网自噬的分子机制  

Molecular Mechanisms of Endoplasmic Reticulum Stress-induced ER-phagy

作　　者：周佳丽 姜虎 蒋丽娜[1,2] ZHOU Jia-Li;JIANG Hu;JIANG Li-Na(Department of Immunology,College of Lab Medicine,Hebei North University,Zhangjiakou 075000,Hebei,China;Institute of Microcirculation,Hebei North University,Zhangjiakou 075000,Hebei,China)

机构地区：[1]河北北方学院医学检验学院免疫教研室,河北张家口075000 [2]河北北方学院微循环研究所,河北张家口075000

出　　处：《中国生物化学与分子生物学报》2024年第6期788-796,共9页Chinese Journal of Biochemistry and Molecular Biology

基　　金：河北省自然科学基金面上项目(No.H2020405023);河北省高等学校科学技术研究项目(No.ZD2020301)资助。

摘　　要：内质网应激是细胞在应对缺氧、营养缺乏等情况时产生的保护性应激反应,通过诱导未折叠蛋白质反应的3条通路来缓解内质网的蛋白质堆积。内质网应激通过内质网自噬受体诱导的内质网自噬,是降解不易被未折叠蛋白质反应途径降解的未折叠或错误折叠的蛋白质,以及恢复内质网形态结构的重要途径。哺乳动物和酵母细胞中存在多种内质网自噬受体,主要功能为促进内质网碎片的形成,并捕获自噬底物,将内质网碎片和未折叠或错误折叠的蛋白质递送至自噬溶酶体中进行降解。每种内质网自噬受体具有独特的结构导致它们捕获自噬底物的方式不尽相同;同时,内质网应激通过不同的途径调控内质网自噬受体的表达和磷酸化。因而,内质网应激通过不同的分子机制激活内质网自噬受体介导的内质网自噬。此外,内质网应激介导的内质网自噬在许多人类疾病的发生发展中发挥重要的作用。阐明内质网应激诱导内质网自噬的具体机制,为内质网自噬相关疾病的防治提供理论依据。因此,本文将综述内质网应激启动哺乳动物细胞中内质网自噬受体FAM134B、RTN3L、SEC62、CCPG1和酵母细胞中内质网自噬受体Atg39、Atg40、Erp1介导的内质网自噬的分子机制,以及内质网应激诱导的内质网自噬与神经退行性疾病和肿瘤等人类疾病的联系,为内质网自噬相关疾病的防治提供新策略。Endoplasmic reticulum stress(ERS)is a protective cellular response that occurs when cells face hypoxia or nutrient deprivation.It alleviates protein accumulation in the endoplasmic reticulum(ER)by the unfolded protein response.Unfolded or misfolded proteins that are not efficiently cleared by the unfolded protein response pathway are degraded by endoplasmic reticulum-phagy(ER-phagy),which is trigged by ERS to restore ER morphology.ER-phagy is mediated by ER-phagy receptors.In mammalian and yeast cells,various ER-phagy receptors exist that promote ER fragment formation,capture autophagic cargos and deliver them to autolysosomes for degradation.Each ER-phagy receptor has unique structural features that determine its mode of cargo capture.Additionally,ERS regulates ER-phagy by mediating the expression and phosphorylation of ER-phagy receptors.Research has shown that ERS-induced ER-phagy plays a crucial role in the pathogenesis of various human diseases.Therefore,elucidating the specific mechanisms underlying ERS-induced ER-phagy provides a theoretical basis for the prevention and treatment of ER-phagy-related diseases.Herein,we review the molecular mechanisms of ERS-induced ER-phagy mediated by ER-phagy receptors in mammals(FAM134B,RTN3L,SEC62,CCPG1)and yeasts(Atg39,Atg40,Erp1),as well as the connection between ERS-induced ER-phagy and human diseases such as neurodegenerative disorders and cancer,aiming to provide new strategies for the prevention and treatment of ER-phagy-related diseases.

关 键 词：内质网应激 内质网自噬 内质网自噬受体 未折叠蛋白质反应 

分 类 号：Q25[生物学—细胞生物学]