线粒体呼吸链酶复合物V缺陷与线粒体病

线粒体呼吸链酶复合物V，也称为ATP合酶，是位于线粒体内膜上的大蛋白复合体，由2个功能性蛋白复合物F0及F1构成。复合物V是线粒体呼吸链的最后一个复合物，在线粒体中通过电化学梯度传递质子，以ADP、Pi及Mg2+为原料合成ATP，为细胞供能。大多数患者新生儿期发病，导致严重脑损害或多脏器损害，病死率很高。主要临床表现为神经肌肉病、心肌病、高乳酸血症及3 甲基戊烯二酸尿症等，因受累器官的不同导致显著的临床异质性。复合物V由16个亚基组成，由线粒体基因与核基因共同编码。迄今，国内外已报道了MT-ATP6、MT-ATP8、ATPAF2、TMEM70、ATP5E基因突变导致的复合物V缺陷。本文总结了线粒体呼吸链复合物V的结构及功能，并对复合物V缺陷的病理、临床表现、诊断、治疗及分子遗传学研究进展进行了综述。

Mitochondrial disorders associated with mitochondrial respiratory chain complex V deficiency

The mammalian mitochondrial ATP synthase,also as known as mitochondrial respiratory chain complex V,is a large protein complex located in the mitochondrial inner membrane,where it catalyzes ATP synthesis from ADP,Pi,and Mg2+ at the expense of an electrochemical gradient of protons generated by the electron transport chain.Complex V is composed of 2 functional domains F0 and F1.The clinical features of patients are significantly heterogeneous depending on the involved organs.Most patients with complex V deficiency had clinical onset in the neonatal period with severe brain damage or multi-organ failure resulting in a high mortality.Neuromuscular disorders,cardiomyopathy,lactic acidosis and 3-methylglutaconic aciduria are common findings.Complex V consists of 16 subunits encoded by both mitochondrial DNA and nuclear DNA.On MT-ATP6,MT-ATP8,ATPAF2,TMEM70 and ATP5E gene of mitochondrial DNA,many mutations associated with Complex V deficiency have been identified.Here,the pathology,clinical features,diagnosis,treatment and molecular genetics of Complex V deficiency were summarized.