Integrative analysis of the mitochondrial proteome in yeast |
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Authors: | Prokisch Holger Scharfe Curt Camp David G Xiao Wenzhong David Lior Andreoli Christophe Monroe Matthew E Moore Ronald J Gritsenko Marina A Kozany Christian Hixson Kim K Mottaz Heather M Zischka Hans Ueffing Marius Herman Zelek S Davis Ronald W Meitinger Thomas Oefner Peter J Smith Richard D Steinmetz Lars M |
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Institution: | 1
Institute of Human Genetics, GSF National Research Center for Environment and Health
Neuherberg
Germany;2
Institute of Human Genetics, Technical University of Munich
Munich
Germany;3
Stanford Genome Technology Center and Department of Biochemistry, Stanford University
Stanford, California
United States of America;4
Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory
Richland, Washington
United States of America |
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Abstract: | In this study yeast mitochondria were used as a model system to apply, evaluate, and integrate different genomic approaches to define the proteins of an organelle. Liquid chromatography mass spectrometry applied to purified mitochondria identified 546 proteins. By expression analysis and comparison to other proteome studies, we demonstrate that the proteomic approach identifies primarily highly abundant proteins. By expanding our evaluation to other types of genomic approaches, including systematic deletion phenotype screening, expression profiling, subcellular localization studies, protein interaction analyses, and computational predictions, we show that an integration of approaches moves beyond the limitations of any single approach. We report the success of each approach by benchmarking it against a reference set of known mitochondrial proteins, and predict approximately 700 proteins associated with the mitochondrial organelle from the integration of 22 datasets. We show that a combination of complementary approaches like deletion phenotype screening and mass spectrometry can identify over 75% of the known mitochondrial proteome. These findings have implications for choosing optimal genome-wide approaches for the study of other cellular systems, including organelles and pathways in various species. Furthermore, our systematic identification of genes involved in mitochondrial function and biogenesis in yeast expands the candidate genes available for mapping Mendelian and complex mitochondrial disorders in humans. |
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