Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria.
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.
Mootha
Vamsi K
VK
MDS Proteomics, Odense 5230, Denmark.
Bunkenborg
Jakob
J
Olsen
Jesper V
JV
Hjerrild
Majbrit
M
Wisniewski
Jacek R
JR
Stahl
Erich
E
Bolouri
Marjan S
MS
Ray
Heta N
HN
Sihag
Smita
S
Kamal
Michael
M
Patterson
Nick
N
Lander
Eric S
ES
Mann
Matthias
M
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
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012333:RNA, Messenger