Integrated Analysis of Protein Composition, Tissue Diversity, and Gene Regulation in Mouse Mitochondria

Cell 115: 629-640. Published: 2003.11.25

Vamsi K. Mootha, Jakob Bunkenborg, Jesper V. Olsen, Majbrit Hjerrild, Jacek R. Wisniewski, Erich Stahl, Marjan S. Bolouri, Heta N. Ray, Smita Sihag, Michael Kamal, Nick Patterson, Eric S. Lander, and Matthias Mann

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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 the 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 a wide battery of tissues reveal sub-networks of mitochondrial genes that share function 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.

Keywords: biogenesis diversity evolution genomics mitochondria mtDNA proteomics


Supplemental Data

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Supplemental Website at Cell
Supplemental Table S1 Supplemental Table S1.xls
Supplemental Table S2 Supplemental Table S2.xls
Supplemental Table S3 Supplemental Table S3.xls
Supplemental Table S4 Supplemental Table S4.xls