Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight Muscles.

Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight Muscles.
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DOI:
10.1016/j.celrep.2017.06.015
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发表时间:
2017-07-05
期刊:
影响因子:
8.8
通讯作者:
Owusu-Ansah E
Owusu-Ansah E
中科院分区:
生物学1区
文献类型:
--
作者:
Garcia CJ;Khajeh J;Coulanges E;Chen EI;Owusu-Ansah E

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果蝇的飞行肌富含线粒体,但线粒体复合物I(CI)在该组织中组装的机制尚未描述。我们报告了果蝇飞行肌肉中CI生物发生的机制,并表明它通过形成~315-,~550-和~815 kDa CI组装中间体进行。此外,我们还为组装过程中的几个CI子单元定义了特定的角色。特别是,我们表明,dNDUFS 5是需要转换成~700 kDa的瞬时CI组装中间体的~815 kDa的组装中间体。重要的是,将dNDUFS 5掺入Cl中对于稳定或促进dNDUFA 10掺入复合物中是必要的。我们的研究结果突出了在果蝇中的CI生物发生的研究,以揭示CI组装在体内的机制的潜力,并建立果蝇作为一个合适的模式生物和资源,以解决有关的问题CI生物发生在人类。
The flight muscles of Drosophila are highly enriched with mitochondria; but the mechanism by which mitochondrial complex I (CI) is assembled in this tissue has not been described. We report the mechanism of CI biogenesis in Drosophila flight muscles; and show that it proceeds via the formation of ~315-, ~550-, and ~815 kDa CI assembly intermediates. Additionally, we define specific roles for several CI subunits in the assembly process. In particular, we show that dNDUFS5 is required for converting an ~700 kDa transient CI assembly intermediate into the ~815 kDa assembly intermediate. Importantly, incorporation of dNDUFS5 into CI is necessary to stabilize or promote incorporation of dNDUFA10 into the complex. Our findings highlight the potential of studies of CI biogenesis in Drosophila to uncover the mechanism of CI assembly in vivo; and establish Drosophila as a suitable model organism and resource for addressing questions relevant to CI biogenesis in humans.
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