线粒体蛋白酶与人类疾病  

Mitochondrial protease and human disease

作　　者：郑斌娇 张煜[1] 杨佳钰 吕斌 ZHENG BinJiao;ZHANG Yu;YANG JiaYu;LU Bin(Department of Cell Biology and Genetics,School of Basic Medical Sciences,Hengyang Medical School,University of South China,Hengyang 421001,China;School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Wenzhou 325035,China;Department of Gastroenterology,The Affiliated Nanhua Hospital of Hengyang Medical School,University of South China,Hengyang 421002,China)

机构地区：[1]南华大学衡阳医学院基础医学院细胞生物学与遗传学教研室,衡阳421001 [2]温州医科大学检验医学院(生命科学学院),温州325035 [3]南华大学衡阳医学院附属南华医院消化内科,衡阳421002

出　　处：《中国科学：生命科学》2023年第10期1345-1360,共16页Scientia Sinica(Vitae)

摘　　要：线粒体是真核细胞的重要细胞器,在能量转换、细胞应激、脂质合成以及细胞凋亡中具有调节作用.许多线粒体蛋白酶参与蛋白质运输、加工激活和降解过程.其中,ATP依赖性的线粒体蛋白酶通过其AAA+结构域(ATP associated multiple activity domain,AAA domain)利用ATP水解来执行线粒体蛋白质质量控制和调节蛋白降解.线粒体蛋白酶活性的改变会导致线粒体功能障碍,从而导致多种人类疾病,包括心血管疾病、神经退行性疾病、衰老和肿瘤等.本文重点综述线粒体蛋白酶1(Lon protease 1,LONP1)、酪蛋白水解蛋白酶P(caseinolytic protease,ClpP)、m-AAA(IMM-embedded AAA face to matrix)和i-AAA(IMM-embedded AAA face to intermembrane space)蛋白酶四种ATP依赖性线粒体蛋白酶及其功能,并阐述其与人类疾病的相关性和临床意义.Mitochondria are important organelles of eukaryotic cells and confer regulatory roles in energy conversion,cellular stress,lipid synthesis,and cell death.A plethora of mitochondrial proteases are involved in protein transport,processing activation and degradation.Among them,adenosine triphosphate ATP-dependent mitochondrial proteases,based on ATP hydrolysis through their Adenosine triphosphatases(ATPases)associated with diverse cellular activities(AAA+)structural domain,the quality control of mitochondrial protein and regulate protein degradation.Alterations in mitochondrial protease activity can lead to mitochondrial dysfunction,thus leading to a variety of human disease,including cardiovascular disease(CVDs),neurodegenerative disease,aging,and tumor.This study provides a systematic review of several well-studied ATP-dependent mitochondrial proteases and explores their functional relevance and clinical implications to human disease.

关 键 词：线粒体 线粒体蛋白酶 线粒体蛋白质质量控制 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]