Mitochondrial copper metabolism and delivery to cytochrome c oxidase.
Mitochondrial copper metabolism and delivery to cytochrome c oxidase.
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DOI：
10.1002/iub.50
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发表时间：
2008-07
期刊：
影响因子：
4.6
通讯作者：
Barrientos, Antoni
中科院分区：
文献类型：
--
作者：
Horn, Darryl;Barrientos, Antoni
金属是所有生物体的基本元素。其中，铜是所需的多种功能，包括线粒体氧化磷酸化和保护氧化应激。在这里，我们将集中描述的途径参与交付铜细胞色素c氧化酶（考克斯），线粒体金属酶作为线粒体呼吸链的末端酶。考克斯的催化核心由三个重复编码的亚基形成，并含有三个铜原子。与亚基2结合的两个铜原子构成CuA位点，其是来自铁细胞色素c的电子的主要受体。第三个铜，CuB，与亚基1的高自旋血红素a3组相关。最近的研究主要是在酿酒酵母中进行的，这些研究为以下方面提供了新的线索：1-用于考克斯代谢的铜的来源; 2-分别参与铜向CuA和CuB位点的直接递送的蛋白Sco 1 p和Cox 11 p的作用; 3-为Sco 1 p和Cox 11 p提供铜的铜伴侣Cox 17 p的作用机制; 4-存在至少四种携带提示金属结合的类似孪生CX 9 C结构域的Cox 17 p同源物，Cox 19 p、Cox 23 p、Pet 191 p和Cmc 1 p，其可能是相同途径的一部分;和5-线粒体膜间隙中存在二硫键中继系统，介导具有保守半胱氨酸基序（如CX 9 C特征）的蛋白质的输入Cox 17 p及其同源物。在线粒体考克斯组装和铜稳态的背景下，不同的途径进行审查和讨论。
Metals are essential elements of all living organisms. Among them, copper is required for a multiplicity of functions including mitochondrial oxidative phosphorylation and protection against oxidative stress. Here we will focus on describing the pathways involved in the delivery of copper to cytochrome c oxidase (COX), a mitochondrial metalloenzyme acting as the terminal enzyme of the mitochondrial respiratory chain. The catalytic core of COX is formed by three mitochondrially-encoded subunits and contains three copper atoms. Two copper atoms bound to subunit 2 constitute the CuA site, the primary acceptor of electrons from ferrocytochrome c. The third copper, CuB, is associated with the high-spin heme a3 group of subunit 1. Recent studies, mostly performed in the yeast Saccharomyces cerevisiae, have provided new clues about 1- the source of the copper used for COX metallation; 2- the roles of Sco1p and Cox11p, the proteins involved in the direct delivery of copper to the CuA and CuB sites, respectively; 3- the action mechanism of Cox17p, a copper chaperone that provides copper to Sco1p and Cox11p; 4- the existence of at least four Cox17p homologues carrying a similar twin CX9C domain suggestive of metal binding, Cox19p, Cox23p, Pet191p and Cmc1p, that could be part of the same pathway; and 5- the presence of a disulfide relay system in the intermembrane space of mitochondria that mediates import of proteins with conserved cysteines motifs such as the CX9C characteristic of Cox17p and its homologues. The different pathways are reviewed and discussed in the context of both mitochondrial COX assembly and copper homeostasis.
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