Definition of a High-Confidence Mitochondrial Proteome at Quantitative Scale.
Definition of a High-Confidence Mitochondrial Proteome at Quantitative Scale.
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DOI：
10.1016/j.celrep.2017.06.014
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发表时间：
2017-06-27
期刊：
影响因子：
8.8
通讯作者：
Warscheid B
中科院分区：
文献类型：
--
作者：
Morgenstern M;Stiller SB;Lübbert P;Peikert CD;Dannenmaier S;Drepper F;Weill U;Höß P;Feuerstein R;Gebert M;Bohnert M;van der Laan M;Schuldiner M;Schütze C;Oeljeklaus S;Pfanner N;Wiedemann N;Warscheid B
线粒体在细胞生物能量学、代谢和信号传导中发挥中心作用，并且它们的功能障碍与许多疾病有关。现有的研究只涵盖了线粒体蛋白质组的一部分，并从相关的馏分核心线粒体蛋白质的分离尚未实现。我们发展了一个综合的实验方法来确定东部线粒体的蛋白质组。我们对线粒体和线粒体相关组分的> 3，300种蛋白质进行了分类，并定义了901种高置信度的线粒体蛋白质，将线粒体蛋白质组扩大了82种。我们的分析包括蛋白质丰度下发酵和nonfermentable增长，submitochondrial定位，单蛋白实验，和亚细胞分类的葡萄球菌相关的馏分。我们确定了呼吸链超复合物，ATP合酶，AAA蛋白酶，线粒体接触位点和嵴组织系统（MICOS），辅酶Q生物合成簇，以及线粒体蛋白质的线粒体相互作用与双重细胞定位。整合蛋白质组为线粒体的生理和病理生理功能及其整合到细胞环境中的表征提供了高置信度的来源。线粒体和相关组分的> 3，300种蛋白质的分类具有绝对定量和拓扑学的高置信度线粒体蛋白质组氧化磷酸化复合物和嵴组织系统的相互作用识别连接呼吸链和AAA质量控制的系统Morgenstern et al.描述了一个整合的细胞器蛋白质组学分析，以确定面包酵母中的线粒体蛋白质组。该研究提供了蛋白质组的定量足迹及其在不同条件下的动力学。这些结果扩展了分配给线粒体的蛋白质组，并为未来的线粒体研究提供了资源。
Mitochondria perform central functions in cellular bioenergetics, metabolism, and signaling, and their dysfunction has been linked to numerous diseases. The available studies cover only part of the mitochondrial proteome, and a separation of core mitochondrial proteins from associated fractions has not been achieved. We developed an integrative experimental approach to define the proteome of east mitochondria. We classified > 3,300 proteins of mitochondria and mitochondria-associated fractions and defined 901 high-confidence mitochondrial proteins, expanding the set of mitochondrial proteins by 82. Our analysis includes protein abundance under fermentable and nonfermentable growth, submitochondrial localization, single-protein experiments, and subcellular classification of mitochondria-associated fractions. We identified mitochondrial interactors of respiratory chain supercomplexes, ATP synthase, AAA proteases, the mitochondrial contact site and cristae organizing system (MICOS), and the coenzyme Q biosynthesis cluster, as well as mitochondrial proteins with dual cellular localization. The integrative proteome provides a high-confidence source for the characterization of physiological and pathophysiological functions of mitochondria and their integration into the cellular environment. Classification of > 3,300 proteins of mitochondria and associated fractions High-confidence mitochondrial proteome with absolute quantification and topology Interactors of oxidative phosphorylation complexes and cristae organizing system Identification of system linking respiratory chain and AAA quality control Morgenstern et al. describe an integrative organelle proteomics analysis to define the mitochondrial proteome in baker’s yeast. The study provides a quantitative footprint of the proteome and its dynamics under different conditions. The results expand the set of proteins assigned to the mitochondria and provide a resource for future mitochondrial research.