Systems Biology | Rare Diseases | Common Diseases | Calcium Uniporter
Systems Biology of the Mitochondrion  

Our lab combines the new tools of genomics with classic biochemistry and physiology to probe mitochondrial physiology. In recent years, we have comprehensively characterized the organelle's proteome to produce an inventory of 1100 proteins we call MitoCarta. We now use large-scale computational analysis in combination with RNAi to systematically elucidate the function of these 1100 proteins. For example, we have performed a large-scale RNA co-expression analysis to spotlight novel mRNA binding proteins that regulate mtDNA gene expression. We have performed large-scale phylogenetic analysis to identify novel proteins required for the assembly and activity of complex I of the respiratory chain. We have also used comparative proteomics to reveal proteins required for mitochondrial calcium uptake. We are currently combining these approaches with small molecule perturbations and global metabolic profiling.


Selected Publications
arrow Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter
Baughman J, Perocchi F, Girgis H, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, Koteliansky V, Mootha VK
Nature, 476(7360):341-5. 2010
arrow MICU1 encodes a mitochondrial EF hand protein required for Ca2+ uptake
Perocchi F, Gohil VK, Girgis H, Bao R., McCombs JE, Palmer AE, Mootha VK.
Nature, 467(7313):291-6. 2010
arrow Discovery of genes essential for heme biosynthesis through large-scale gene expression analysis
Nilsson R, Schultz IJ, Pierce EL, Soltis KA, Naranuntarat A, Ward DM, Baughman JM, Paradkar PN, Kingsley PD, Culotta VC, Kaplan J, Palis J, Paw BH, Mootha VK.
Cell Metabolism 10:119-30. 2009
arrow A computational screen for regulators of oxidative phosphorylation Implicates SLIRP in mitochondrial RNA homeostasis
Baughman JM, Nilsson R, Gohil VM, Arlow DH, Gauhar Z, Mootha VK.
PLoS Genetics 5(8): e10000590. 2009
arrow A mitochondrial protein compendium elucidates complex I disease biology
Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB, Ong SE, Walford GA, Sugiana C, Boneh A, Chen WK, Hill DE, Vidal M, Evans JG, Thorburn DR, Carr SA, Mootha VK.
Cell 134:112-23. 2008
arrow Systematic identification of human mitochondrial disease genes through integrative genomics
Calvo S, Jain M, XieX , Sheth SA, Goldberger O, Chang B, Spinazzola A, Zeviani M, Carr SA, Mootha VK.
Nature Genetics 38:576-582. 2006