title: Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria.
abstract: Mitochondria are tailored to meet the metabolic and signaling needs of each cell. To explore its molecular composition, we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver and combined the results with existing gene annotations to produce a list of 591 mitochondrial proteins, including 163 proteins not previously associated with this organelle. The protein expression data were largely concordant with large-scale surveys of RNA abundance and both measures indicate tissue-specific differences in organelle composition. RNA expression profiles across tissues revealed networks of mitochondrial genes that share functional and regulatory mechanisms. We also determined a larger "neighborhood" of genes whose expression is closely correlated to the mitochondrial genes. The combined analysis identifies specific genes of biological interest, such as candidates for mtDNA repair enzymes, offers new insights into the biogenesis and ancestry of mammalian mitochondria, and provides a framework for understanding the organelle's contribution to human disease.
authors.affiliation: MDS Proteomics, Odense 5230, Denmark.
authors.forename: Vamsi K
authors.initials: VK
authors.lastname: Mootha
authors.forename: Jakob
authors.initials: J
authors.lastname: Bunkenborg
authors.forename: Jesper V
authors.initials: JV
authors.lastname: Olsen
authors.forename: Majbrit
authors.initials: M
authors.lastname: Hjerrild
authors.forename: Jacek R
authors.initials: JR
authors.lastname: Wisniewski
authors.forename: Erich
authors.initials: E
authors.lastname: Stahl
authors.forename: Marjan S
authors.initials: MS
authors.lastname: Bolouri
authors.forename: Heta N
authors.initials: HN
authors.lastname: Ray
authors.forename: Smita
authors.initials: S
authors.lastname: Sihag
authors.forename: Michael
authors.initials: M
authors.lastname: Kamal
authors.forename: Nick
authors.initials: N
authors.lastname: Patterson
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
mesh_terms: D000818:Animals; D002460:Cell Line; D019069:Cell Respiration / Q000235:genetics; D016172:DNA Fingerprinting; D004272:DNA, Mitochondrial / Q000032:analysis* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D024101:Mitochondrial Proteins / Q000032:analysis* / Q000235:genetics; D010085:Oxidative Phosphorylation; D040901:Proteomics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012333:RNA, Messenger