A cluster of metabolic defects caused by mutation in a mitochondrial tRNA
A cluster of metabolic defects caused by mutation in a mitochondrial tRNA
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DOI：
10.1126/science.1102521
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发表时间：
2004-11-12
期刊：
影响因子：
56.9
通讯作者：
Lifton, RP
中科院分区：
文献类型：
--
作者：
Wilson, FH;Hariri, A;Lifton, RP
高血压和血脂异常是动脉粥样硬化的危险因素，并且同时发生的概率比预期的偶然程度更高。尽管这种聚类表明存在共同的因果关系，但统一因素仍然未知。我们描述了一个患有高血压、高胆固醇血症和低镁血症等综合症的大家族。每种表型都在母系上传递，其模式表明线粒体遗传。对母系线粒体基因组的分析发现了同质突变，即线粒体转移 RNA(Ite) 反密码子的 S' 处的尿苷被胞苷取代。由于其在稳定反密码子环中的作用，该位置的尿苷在转移 RNA 中几乎是不变的。鉴于已知线粒体功能会随着衰老而丧失，这些发现可能对这些代谢紊乱的常见聚集具有影响。
Hypertension and dyslipidemia are risk factors for atherosclerosis and occur together more often than expected by chance. Although this clustering suggests shared causation, unifying factors remain unknown. We describe a large kindred with a syndrome including hypertension, hypercholesterolemia, and hypomagnesemia. Each phenotype is transmitted on the maternal lineage with a pattern indicating mitochondrial inheritance. Analysis of the mitochondrial genome of the maternal lineage identified a homoplasmic mutation substituting cytidine for uridine immediately S' to the mitochondrial transfer RNA(Ite) anticodon. Uridine at this position is nearly invariate among transfer RNAs because of its role in stabilizing the anticodon loop. Given the known loss of mitochondrial function with aging, these findings may have implications for the common clustering of these metabolic disorders.