title: Integrative analysis of the mitochondrial proteome in yeast.
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.
authors.affiliation: Institute of Human Genetics, GSF National Research Center for Environment and Health, Neuherberg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
authors.forename: Curt
authors.initials: C
authors.lastname: Scharfe
authors.forename: David G
authors.initials: DG
authors.lastname: Camp
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Xiao
authors.forename: Lior
authors.initials: L
authors.lastname: David
authors.forename: Christophe
authors.initials: C
authors.lastname: Andreoli
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Monroe
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Moore
authors.forename: Marina A
authors.initials: MA
authors.lastname: Gritsenko
authors.forename: Christian
authors.initials: C
authors.lastname: Kozany
authors.forename: Kim K
authors.initials: KK
authors.lastname: Hixson
authors.forename: Heather M
authors.initials: HM
authors.lastname: Mottaz
authors.forename: Hans
authors.initials: H
authors.lastname: Zischka
authors.forename: Marius
authors.initials: M
authors.lastname: Ueffing
authors.forename: Zelek S
authors.initials: ZS
authors.lastname: Herman
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Davis
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Oefner
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
mesh_terms: D005591:Chemical Fractionation; D002853:Chromatography, Liquid / Q000379:methods; D020869:Gene Expression Profiling; D016678:Genome; D013058:Mass Spectrometry / Q000379:methods; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D010641:Phenotype; D040901:Proteomics / Q000379:methods*; D012680:Sensitivity and Specificity; D015003:Yeasts
chemical_list: D024101:Mitochondrial Proteins