Dubot A, Godinot C, Dumur V, Sablonnière B, Stojkovic T, Cuisset J M, Vojtiskova A, Pecina P, Jesina P, Houstek J
Centre National de la Recherche Scientifique, Université Claude Bernard de Lyon I, 69622 Villeurbanne France.
Biochem Biophys Res Commun. 2004 Jan 16;313(3):687-93. doi: 10.1016/j.bbrc.2003.12.013.
A maternally inherited and practically homoplasmic mitochondrial (mtDNA) mutation, 8527A>G, changing the initiation codon AUG into GUG, normally coding for a valine, was observed in the ATP6 gene encoding the ATPase subunit a. No alternate Met codon could replace the normal translational initiator. The patient harboring this mutation exhibited clinical symptoms suggesting a mitochondrial disease but his mother who carried the same mtDNA mutation was healthy. The mutation was absent from 100 controls and occurred once amongst 44 patients suspected of Leber Hereditary Optic Neuropathy (LHON) but devoid of typical LHON mutations. In patient fibroblasts, no effect of 8527A>G mutation could be demonstrated on the biosynthesis of mtDNA-encoded proteins, on size and the content of ATPase subunit a, on ATP hydrolysis and on mitochondrial membrane potential. In addition, ATP synthesis was barely decreased. Therefore, GUG is a functional initiation codon for the human ATP6 gene.
在编码ATP酶亚基a的ATP6基因中，观察到一种母系遗传且几乎同质的线粒体（mtDNA）突变，8527A>G，该突变将起始密码子AUG变为GUG，正常情况下GUG编码缬氨酸。没有其他替代的Met密码子可以取代正常的翻译起始密码子。携带这种突变的患者表现出提示线粒体疾病的临床症状，但携带相同mtDNA突变的母亲却很健康。100名对照中未发现该突变，在44名疑似患有Leber遗传性视神经病变（LHON）但缺乏典型LHON突变的患者中仅出现过一次。在患者成纤维细胞中，8527A>G突变对mtDNA编码蛋白的生物合成、ATP酶亚基a的大小和含量、ATP水解以及线粒体膜电位均未产生影响。此外，ATP合成仅略有下降。因此，GUG是人类ATP6基因的一个功能性起始密码子。
