MITRAC7 Acts as a COX1-Specific Chaperone and Reveals a Checkpoint during Cytochrome c Oxidase Assembly
MITRAC7 Acts as a COX1-Specific Chaperone and Reveals a Checkpoint during Cytochrome c Oxidase Assembly
复制标题
DOI：
10.1016/j.celrep.2015.08.009
复制
发表时间：
2015-09-08
期刊：
影响因子：
8.8
通讯作者：
Rehling, Peter
中科院分区：
文献类型：
--
作者：
Dennerlein, Sven;Oeljeklaus, Silke;Rehling, Peter
细胞色素c氧化酶是呼吸链的末端酶，由线粒体和核编码的亚基组装而成。MITRAC复合物代表该过程中的中央组装中间体，因为它接收输入的亚基并调节COX1 mRNA的线粒体翻译。促进和调节MITRAC下游组装进展的分子过程仍然未知。在这里，我们确定MITRAC 7作为一种晚期形式的MITRAC的组成部分，并作为COX 1特异性伴侣。MITRAC 7是细胞色素c氧化酶生物合成所必需的。令人惊讶的是，MITRAC 7的缺失或其量的增加导致人类细胞中的选择性细胞色素c氧化酶缺乏。我们证明，增加MITRAC 7水平稳定和陷阱COX1在MITRAC，阻止在组装过程中的进展。相反，MITRAC 7缺陷导致新合成的COX 1的周转。因此，MITRAC 7通过稳定组装中间体中新合成的COX 1来影响生物合成途径，同时防止周转。
Cytochrome c oxidase, the terminal enzyme of the respiratory chain, is assembled from mitochondria- and nuclear-encoded subunits. The MITRAC complex represents the central assembly intermediate during this process as it receives imported subunits and regulates mitochondrial translation of COX1 mRNA. The molecular processes that promote and regulate the progression of assembly downstream of MITRAC are still unknown. Here, we identify MITRAC7 as a constituent of a late form of MITRAC and as a COX1-specific chaperone. MITRAC7 is required for cytochrome c oxidase biogenesis. Surprisingly, loss of MITRAC7 or an increase in its amount causes selective cytochrome c oxidase deficiency in human cells. We demonstrate that increased MITRAC7 levels stabilize and trap COX1 in MITRAC, blocking progression in the assembly process. In contrast, MITRAC7 deficiency leads to turnover of newly synthesized COX1. Accordingly, MITRAC7 affects the biogenesis pathway by stabilizing newly synthesized COX1 in assembly intermediates, concomitantly preventing turnover.