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首页> 外文期刊>Molecular and Cellular Biology >Mammalian Copper Chaperone Cox17p Has an Essential Role in Activation of Cytochrome c Oxidase and Embryonic Development
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Mammalian Copper Chaperone Cox17p Has an Essential Role in Activation of Cytochrome c Oxidase and Embryonic Development

机译：哺乳动物铜伴侣Cox17p在激活细胞色素c氧化酶和胚胎发育中具有重要作用。

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Cox17p is essential for the assembly of functional cytochrome c oxidase (CCO) and for delivery of copper ions to the mitochondrion for insertion into the enzyme in yeast. Although this small protein has already been cloned or purified from humans, mice, and pigs, the function of Cox17p in the mammalian system has not yet been elucidated. In vitro biochemical data for mammalian Cox17p indicate that the copper binds to the sequence -KPCCAC-. Although mouse embryos homozygous for COX17 disruption die between embryonic days E8.5 and E10, they develop normally until E6.5. This phenotype is strikingly similar to embryos of Ctr1(?/?), a cell surface copper transporter, in its lethality around the time of gastrulation. COX17-deficient embryos exhibit severe reductions in CCO activity at E6.5. Succinate dehydrogenase activity and immunoreactivities for anti-COX subunit antibodies were normal in the COX17(?/?) embryos, indicating that this defect was not caused by the deficiency of other complexes and/or subunits but was caused by impaired CCO activation by Cox17p. Since other copper chaperone (Atox1 and CCS)-deficient mice show a more moderate defect, the disruption of the COX17 locus causes the expression of only the phenotype of Ctr1(?/?). We found that the activity of lactate dehydrogenase was also normal in E6.5 embryos, implying that the activation of CCO by Cox17p may not be essential to the progress of embryogenesis before gastrulation.
机译：Cox17p对于功能性细胞色素 c 氧化酶（CCO）的组装以及将铜离子传递到线粒体以插入酵母中的酶至关重要。尽管已经从人，小鼠和猪中克隆或纯化了这种小蛋白，但尚未阐明Cox17p在哺乳动物系统中的功能。哺乳动物Cox17p的体外生化数据表明铜与序列-KPCCAC-结合。尽管对 COX17 破坏纯合的小鼠胚胎在胚胎E8.5和E10天之间死亡，但它们正常发育直至E6.5。这种表型与细胞表面铜转运蛋白Ctr1（α/β）的胚芽惊人地相似，其在致死前后的致死率非常高。 COX17 缺陷的胚胎在E6.5时会严重降低CCO活性。琥珀酸脱氢酶活性和抗COX亚基抗体的免疫反应性在 COX17 （？/？）胚胎中正常，这表明该缺陷不是由其他复合物和/或亚基的缺乏引起的，而是由Cox17p削弱了CCO激活。由于其他铜伴侣蛋白（Atox1和CCS）缺陷小鼠表现出更为中等的缺陷，因此 COX17 基因座的破坏仅导致Ctr1（？/？）表型的表达。我们发现乳酸脱氢酶的活性在E6.5胚胎中也是正常的，这暗示着Cox17p对CCO的激活可能对精胃前胚胎发生的进展不是必不可少的。

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