Role of adenine nucleotide translocator 1 in mtDNA maintenance
Role of adenine nucleotide translocator 1 in mtDNA maintenance
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DOI：
10.1126/science.289.5480.782
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发表时间：
2000-08-04
期刊：
影响因子：
56.9
通讯作者：
Suomalainen, A
中科院分区：
文献类型：
--
作者：
Kaukonen, J;Juselius, JK;Suomalainen, A
常染色体显性进行性眼外肌麻痹是一种罕见的人类疾病，显示孟德尔遗传模式，但其特征是大规模线粒体DNA（mtDNA）缺失。我们已经确定了两个杂合错义突变的核基因编码的心脏/骨骼肌亚型的腺嘌呤核苷酸转运蛋白（ANT 1）在五个家庭和一个散发性患者。熟悉的突变取代高度保守的丙氨酸在位置114的ANT 1蛋白的脯氨酸。酵母中的类似突变导致呼吸缺陷。这些结果表明，ANT在线粒体DNA的维护中发挥作用，线粒体疾病可能是由显性机制引起的。
Autosomal dominant progressive external ophthalmoplegia is a rare human disease that shows a Mendelian inheritance pattern, but is characterized by Large-scale mitochondrial DNA (mtDNA) deletions. We have identified two heterozygous missense mutations in the nuclear gene encoding the heart/skeletal muscle isoform of the adenine nucleotide translocator (ANT1) in five families and one sporadic patient. The familiar mutation substitutes a proline for a highly conserved alanine at position 114 in the ANT1 protein. The analogous mutation in yeast caused a respiratory defect. These results indicate that ANT has a role in mtDNA maintenance and that a mitochondrial disease can be caused by a dominant mechanism.