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MITRAC15/COA1 promotes mitochondrial translation in a ND2 ribosome-nascent chain complex.
EMBO Reports ( IF 7.7 ) Pub Date : 2019-11-13 , DOI: 10.15252/embr.201948833
Cong Wang 1, 2 , Ricarda Richter-Dennerlein 1, 2 , David Pacheu-Grau 1 , Fan Liu 3 , Ying Zhu 3 , Sven Dennerlein 1 , Peter Rehling 1, 2, 4
Affiliation  

The mitochondrial genome encodes for thirteen core subunits of the oxidative phosphorylation system. These proteins assemble with imported proteins in a modular manner into stoichiometric enzyme complexes. Assembly factors assist in these biogenesis processes by providing co-factors or stabilizing transient assembly stages. However, how expression of the mitochondrial-encoded subunits is regulated to match the availability of nuclear-encoded subunits is still unresolved. Here, we address the function of MITRAC15/COA1, a protein that participates in complex I biogenesis and complex IV biogenesis. Our analyses of a MITRAC15 knockout mutant reveal that MITRAC15 is required for translation of the mitochondrial-encoded complex I subunit ND2. We find that MITRAC15 is a constituent of a ribosome-nascent chain complex during ND2 translation. Chemical crosslinking analyses demonstrate that binding of the ND2-specific assembly factor ACAD9 to the ND2 polypeptide occurs at the C-terminus and thus downstream of MITRAC15. Our analyses demonstrate that expression of the founder subunit ND2 of complex I undergoes regulation. Moreover, a ribosome-nascent chain complex with MITRAC15 is at the heart of this process.

中文翻译:

MITRAC15/COA1 促进 ND2 核糖体-新生链复合物中的线粒体翻译。

线粒体基因组编码氧化磷酸化系统的十三个核心亚基。这些蛋白质以模块化方式与进口蛋白质组装成化学计量酶复合物。装配因子通过提供辅助因子或稳定瞬时装配阶段来协助这些生物发生过程。然而,如何调节线粒体编码亚基的表达以匹配核编码亚基的可用性仍未解决。在这里,我们讨论了 MITRAC15/COA1 的功能,这是一种参与复杂 I 生物发生和复杂 IV 生物发生的蛋白质。我们对 MITRAC15 敲除突变体的分析表明,MITRAC15 是翻译线粒体编码复合物 I 亚基 ND2 所必需的。我们发现 MITRAC15 是 ND2 翻译过程中核糖体新生链复合物的组成部分。化学交联分析表明,ND2 特异性装配因子 ACAD9 与 ND2 多肽的结合发生在 C 端,因此位于 MITRAC15 的下游。我们的分析表明复合物 I 的创始人亚基 ND2 的表达受到调节。此外,带有 MITRAC15 的核糖体新生链复合物是该过程的核心。
更新日期:2020-01-07
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