title: Assessing systems properties of yeast mitochondria through an interaction map of the organelle.
abstract: Mitochondria carry out specialized functions; compartmentalized, yet integrated into the metabolic and signaling processes of the cell. Although many mitochondrial proteins have been identified, understanding their functional interrelationships has been a challenge. Here we construct a comprehensive network of the mitochondrial system. We integrated genome-wide datasets to generate an accurate and inclusive mitochondrial parts list. Together with benchmarked measures of protein interactions, a network of mitochondria was constructed in their cellular context, including extra-mitochondrial proteins. This network also integrates data from different organisms to expand the known mitochondrial biology beyond the information in the existing databases. Our network brings together annotated and predicted functions into a single framework. This enabled, for the entire system, a survey of mutant phenotypes, gene regulation, evolution, and disease susceptibility. Furthermore, we experimentally validated the localization of several candidate proteins and derived novel functional contexts for hundreds of uncharacterized proteins. Our network thus advances the understanding of the mitochondrial system in yeast and identifies properties of genes underlying human mitochondrial disorders.
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Perocchi
authors.forename: Lars J
authors.initials: LJ
authors.lastname: Jensen
authors.forename: Julien
authors.initials: J
authors.lastname: Gagneur
authors.forename: Uwe
authors.initials: U
authors.lastname: Ahting
authors.forename: Christian
authors.initials: C
authors.lastname: von Mering
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
mesh_terms: D004198:Disease Susceptibility; D019143:Evolution, Molecular; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D017385:Sequence Homology
chemical_list: D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins