线粒体蛋白酶与人类疾病

Mitochondrial protease and human disease

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.