Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context

作者：Marcel Morgenstern, Christian D. Peikert, Philipp Lübbert, Ida Suppanz, Cinzia Klemm, Oliver Alka, Conny Steiert, Nataliia Naumenko, Alexander Benjamin Schendzielorz, Laura Melchionda, Wignand W. D. Mühlhäuser, Bettina Liebowitz Knapp, Jakob D. Busch, Sebastian B. Stiller, Stefan Dannenmaier, Caroline Lindau, Mariya Licheva, Christopher Eickhorst, Riccardo Galbusera, Ralf M. Zerbes, Michael T. Ryan, Claudine Kraft, Vera Kozjak‐Pavlovic, Friedel Drepper, Sven Dennerlein, Silke Oeljeklaus, Nikolaus Pfanner, Nils Wiedemann, Bettina Warscheid · 发表于：Cell Metabolism · 年份：2021 · DOI：10.1016/j.cmet.2021.11.001 · 被引用次数：362 · 研究领域：Mitochondrial Function and Pathology、ATP Synthase and ATPases Research、Ubiquitin and proteasome pathways

Mitochondria are key organelles for cellular energetics, metabolism, signaling, and quality control and have been linked to various diseases. Different views exist on the composition of the human mitochondrial proteome. We classified >8,000 proteins in mitochondrial preparations of human cells and defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). We identified interactors of translocases, respiratory chain, and ATP synthase assembly factors. The abundance of MitoCoP proteins covers six orders of magnitude and amounts to 7% of the cellular proteome with the chaperones HSP60-HSP10 being the most abundant mitochondrial proteins. MitoCoP dynamics spans three orders of magnitudes, with half-lives from hours to months, and suggests a rapid regulation of biosynthesis and assembly processes. 460 MitoCoP genes are linked to human diseases with a strong prevalence for the central nervous system and metabolism. MitoCoP will provide a high-confidence resource for placing dynamics, functions, and dysfunctions of mitochondria into the cellular context.