Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function.
Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function.
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线粒体蛋白质相互作用图谱确定呼吸链功能的调节因子
DOI：
10.1016/j.molcel.2016.06.033
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发表时间：
2016-08-18
期刊：
影响因子：
16
通讯作者：
Pagliarini DJ
中科院分区：
文献类型：
--
作者：
Floyd BJ;Wilkerson EM;Veling MT;Minogue CE;Xia C;Beebe ET;Wrobel RL;Cho H;Kremer LS;Alston CL;Gromek KA;Dolan BK;Ulbrich A;Stefely JA;Bohl SL;Werner KM;Jochem A;Westphall MS;Rensvold JW;Taylor RW;Prokisch H;Kim JP;Coon JJ;Pagliarini DJ
线粒体在许多细胞过程中是必不可少的，然而它们的数百种蛋白质缺乏强大的功能注释。为了揭示这些蛋白质(称为MXPs)的新功能，我们使用亲和富集质谱评估了50个精选MXPs的特定条件下的蛋白质-蛋白质相互作用。我们的数据将MXP与不同的线粒体过程联系起来，包括呼吸链功能的多个方面。在这些观察的基础上，我们验证了C17orf89是复杂的I(CI)组装因子。C17orf89基因的缺失显著降低了CI活性，在一例尚未解决的CI缺乏症中发现了它的缺失。我们同样发现LYRM5与电子转移黄素蛋白相互作用并脱黄，黄素蛋白将电子传递到辅酶Q(CoQ)。最后，我们鉴定了一个动态的人类辅酶Q生物合成复合体，涉及多个MXP，我们使用纯化的成分映射其拓扑结构。总体而言，我们的数据为呼吸链相关活动提供了新的机械性见解，并优先考虑数百种额外的相互作用，以进一步探索线粒体蛋白质的功能。线粒体是重要的细胞器，然而它们的数百种蛋白质缺乏强大的功能特征。Floyd等人。定义50个这样的蛋白质的相互作用伙伴，提供关于它们在线粒体中的作用的假设。特别是，他们的工作为呼吸链活动提供了新的机制，这些活动与复合体I、电子转移黄素蛋白和辅酶Q有关。
Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal new functions for these proteins (termed MXPs) we assessed condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our data connect MXPs to diverse mitochondrial processes, including multiple aspects of respiratory chain function. Building upon these observations, we validated C17orf89 as a complex I (CI) assembly factor. Disruption of C17orf89 markedly reduced CI activity, and its depletion is found in an unresolved case of CI deficiency. We likewise discovered that LYRM5 interacts with and deflavinates the electron transferring flavoprotein that shuttles electrons to coenzyme Q (CoQ). Finally, we identified a dynamic human CoQ biosynthetic complex involving multiple MXPs whose topology we map using purified components. Collectively, our data lend new mechanistic insight into respiratory chain-related activities and prioritize hundreds of additional interactions for further exploration of mitochondrial protein function. Mitochondria are essential organelles, yet hundreds of their proteins lack robust functional characterization. Floyd et al. define interaction partners for 50 such proteins, providing hypotheses about their roles in mitochondria. In particular, their work lends new mechanistic insight into respiratory chain activities related to complex I, the electron transferring flavoprotein, and coenzyme Q.