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An antibody toolbox to track complex I assembly defines AIF’s mitochondrial function
Journal of Cell Biology ( IF 7.4 ) Pub Date : 2020-09-16 , DOI: 10.1083/jcb.202001071
Anjaneyulu Murari 1 , Shauna-Kay Rhooms 1 , Naga Sri Goparaju 1 , Maximino Villanueva 1 , Edward Owusu-Ansah 1, 2
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An ability to comprehensively track the assembly intermediates (AIs) of complex I (CI) biogenesis in Drosophila will enable the characterization of the precise mechanism(s) by which various CI regulators modulate CI assembly. Accordingly, we generated 21 novel antibodies to various mitochondrial proteins and used this resource to characterize the mechanism by which apoptosis-inducing factor (AIF) regulates CI biogenesis by tracking the AI profile observed when AIF expression is impaired. We find that when the AIF–Mia40 translocation complex is disrupted, the part of CI that transfers electrons to ubiquinone is synthesized but fails to progress in the CI biosynthetic pathway. This is associated with a reduction in intramitochondrial accumulation of the Mia40 substrate, MIC19. Importantly, knockdown of either MIC19 or MIC60, components of the mitochondrial contact site and cristae organizing system (MICOS), fully recapitulates the AI profile observed when AIF is inhibited. Thus, AIF’s effect on CI assembly is principally due to compromised intramitochondrial transport of the MICOS complex.

中文翻译:

追踪复合物 I 组装的抗体工具箱定义了 AIF 的线粒体功能

全面跟踪果蝇中复合物 I (CI) 生物发生的组装中间体 (AI) 的能力将能够表征各种 CI 调节剂调节 CI 组装的精确机制。因此,我们针对各种线粒体蛋白产生了 21 种新型抗体,并利用该资源通过跟踪 AIF 表达受损时观察到的 AI 谱来表征凋亡诱导因子 (AIF) 调节 CI 生物发生的机制。我们发现,当 AIF-Mia40 易位复合物被破坏时,CI 将电子转移到泛醌的部分被合成,但无法在 CI 生物合成途径中进行。这与 Mia40 底物 MIC19 线粒体内积累的减少有关。重要的是,抑制 MIC19 或 MIC60(线粒体接触位点和嵴组织系统 (MICOS) 的组成部分)完全重现了抑制 AIF 时观察到的 AI 特征。因此,AIF 对 CI 组装的影响主要是由于 MICOS 复合体的线粒体内运输受损。
更新日期:2020-09-16
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