Baranowska Emilia, Rytka Joanna, Kucharczyk Róża
Zakład Genetyki, Instytut Biochemii i Biofizyki Polskiej Akademii Nauk, Warszawa.
Postepy Biochem. 2018 Dec 29;64(4):304-317. doi: 10.18388/pb.2018_144.
ATP synthase is the last enzyme of the OXPHOS system synthesizing ATP. Mutations in either mitochondrial or nuclear genes encoding subunits of this enzyme (17 polypeptides) cause neurodegenerative diseases. The ATP synthase subunits 8 (ATP8, alias A6L) and a (ATP6) are encoded by the MT-ATP8 and MT-ATP6 mitochondrial genes, respectively. 17 diseases associated mutations were identified in five nuclear genes coding for subunits of this enzyme. 58 mutations were described in the MT-ATP6 and MT-ATP8 genes, among them 36 were deposited in MITOMAP database. For most of them neither their pathogenic character nor the mechanisms are known. This review summarizes what is known about the molecular basis of the ATP synthase deficiencies. We review the mutations in the ATP synthase genes as well as biochemical data obtained from studies of patient's cells and cybrid or yeast models. We include yeast research about drugs selection and their mechanism of action. Moreover we position the mutations into a recently published structural model of the Fo complex and discuss their structural/functional consequences.
ATP合酶是氧化磷酸化系统中合成ATP的最后一种酶。编码该酶亚基（17种多肽）的线粒体或核基因发生突变会导致神经退行性疾病。ATP合酶亚基8（ATP8，别名A6L）和亚基a（ATP6）分别由线粒体基因MT - ATP8和MT - ATP6编码。在编码该酶亚基的五个核基因中鉴定出17种与疾病相关的突变。MT - ATP6和MT - ATP8基因中描述了58种突变，其中36种已存入MITOMAP数据库。对于大多数突变，其致病特性和机制均未知。本综述总结了关于ATP合酶缺陷分子基础的已知信息。我们回顾了ATP合酶基因中的突变以及从患者细胞、胞质杂种或酵母模型研究中获得的生化数据。我们纳入了关于酵母药物筛选及其作用机制的研究。此外，我们将突变定位到最近发表的F₀复合体结构模型中，并讨论其结构/功能后果。
