Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin
Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin
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DOI：
10.1038/ng0897-345
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发表时间：
1997-08-01
期刊：
影响因子：
30.8
通讯作者：
Koenig, M
中科院分区：
文献类型：
--
作者：
Koutnikova, H;Campuzano, V;Koenig, M
Friedreich 的共济失调是由于编码 frataxin (FRDA) 的基因功能缺失突变所致。 Frataxin 是一种功能未知的蛋白质。原位杂交分析表明，小鼠 frataxin 表达与神经变性的主要部位密切相关，但表达模式比疾病病理学预期的更广泛。 Frataxin mRNA 主要在代谢率较高的组织中表达，包括肝脏、肾脏、棕色脂肪和心脏。我们发现小鼠和酵母 frataxin 同源物在其 N 末端结构域中含有潜在的线粒体靶向序列，并且酵母基因的破坏会导致线粒体功能障碍。最后，标记实验证明人 frataxin 与线粒体蛋白共定位。因此，弗里德赖希共济失调是一种由核基因组突变引起的线粒体疾病。
Friedreich's ataxia is due to loss of function mutations in the gene encoding frataxin (FRDA). Frataxin is a protein of unknown function. In situ hybridization analyses revealed that mouse frataxin expression correlates well with the main site of neurodegeneration, but the expression pattern is broader than expected from the pathology of the disease. Frataxin mRNA is predominantly expressed in tissues with a high metabolic rate, including liver, kidney, brown fat and heart. We found that mouse and yeast frataxin homologues contain a potential mitochondrial targeting sequence in their N-terminal domains and that disruption of the yeast gene results in mitochondrial dysfunction. Finally, tagging experiments demonstrate that human frataxin co-localizes with a mitochondrial protein. Friedreich's ataxia is therefore a mitochondrial disease caused by a mutation in the nuclear genome.