Morgenstern Marcel, Stiller Sebastian B, Lübbert Philipp, Peikert Christian D, Dannenmaier Stefan, Drepper Friedel, Weill Uri, Höß Philipp, Feuerstein Reinhild, Gebert Michael, Bohnert Maria, van der Laan Martin, Schuldiner Maya, Schütze Conny, Oeljeklaus Silke, Pfanner Nikolaus, Wiedemann Nils, Warscheid Bettina
Institute of Biology II, Biochemistry and Functional Proteomics, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
Cell Rep. 2017 Jun 27;19(13):2836-2852. doi: 10.1016/j.celrep.2017.06.014.
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 yeast 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.
线粒体在细胞生物能量学、新陈代谢及信号传导中发挥核心作用，其功能障碍与多种疾病相关。现有研究仅涵盖了线粒体蛋白质组的一部分，尚未实现将核心线粒体蛋白与相关组分分离。我们开发了一种综合实验方法来定义酵母线粒体蛋白质组。我们对线粒体及线粒体相关组分中的3300多种蛋白质进行了分类，确定了901种高可信度的线粒体蛋白，使线粒体蛋白的数量增加了82种。我们的分析包括可发酵和不可发酵生长条件下的蛋白质丰度、亚线粒体定位、单蛋白实验以及线粒体相关组分的亚细胞分类。我们鉴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）以及辅酶Q生物合成簇的线粒体相互作用蛋白，以及具有双重细胞定位的线粒体蛋白。该综合蛋白质组为表征线粒体的生理和病理生理功能及其与细胞环境的整合提供了高可信度的资源。
