细胞色素c氧化酶
生物
电子传递复合物IV
线粒体
蛋白质亚单位
线粒体生物发生
细胞生物学
酿酒酵母
选择性氧化酶
酵母
线粒体呼吸链
生物化学
转运蛋白
呼吸链
生物发生
基因
作者
Abhinav B. Swaminathan,Shivatheja Soma,Alison C. Vicary,Mohammad Zulkifli,Harman Kaur,Vishal M. Gohil
出处
期刊:Genetics
[Oxford University Press]
日期:2022-06-06
卷期号:221 (4)
被引量:4
标识
DOI:10.1093/genetics/iyac090
摘要
Abstract Cytochrome c oxidase (CcO) is a multimeric copper-containing enzyme of the mitochondrial respiratory chain that powers cellular energy production. The two core subunits of cytochrome c oxidase, Cox1 and Cox2, harbor the catalytic CuB and CuA sites, respectively. Biogenesis of each copper site occurs separately and requires multiple proteins that constitute the mitochondrial copper delivery pathway. Currently, the identity of all the members of the pathway is not known, though several evolutionarily conserved twin CX9C motif-containing proteins have been implicated in this process. Here, we performed a targeted yeast suppressor screen that placed Coa4, a twin CX9C motif-containing protein, in the copper delivery pathway to the Cox1 subunit. Specifically, we show that overexpression of Cox11, a copper metallochaperone required for the formation of CuB site, can restore Cox1 abundance, cytochrome c oxidase assembly, and mitochondrial respiration in coa4Δ cells. This rescue is dependent on the copper-coordinating cysteines of Cox11. The abundance of Coa4 and Cox11 in mitochondria is reciprocally regulated, further linking Coa4 to the CuB site biogenesis. Additionally, we find that coa4Δ cells have reduced levels of copper and exogenous copper supplementation can partially ameliorate its respiratory-deficient phenotype, a finding that connects Coa4 to cellular copper homeostasis. Finally, we demonstrate that human COA4 can replace the function of yeast Coa4 indicating its evolutionarily conserved role. Our work provides genetic evidences for the role of Coa4 in the copper delivery pathway to the CuB site of cytochrome c oxidase.
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