The Mitochondrial Proteome and Human Disease
Open accessAbstract
For nearly three decades, the sequence of the human mitochondrial genome (mtDNA) has provided a molecular framework for understanding maternally inherited diseases. However, the vast majority of human mitochondrial disorders are caused by nuclear genome defects, which is not surprising since the mtDNA encodes only 13 proteins. Advances in genomics, mass spectrometry, and computation have only recently made it possible to systematically identify the complement of over 1,000 proteins that comprise the mammalian mitochondrial proteome. Here, we review recent progress in characterizing the mitochondrial proteome and highlight insights into its complexity, tissue heterogeneity, evolutionary origins, and biochemical versatility. We then discuss how this proteome is being used to discover the genetic basis of respiratory chain disorders as well as to expand our definition of mitochondrial disease. Finally, we explore future prospects and challenges for using the mitochondrial proteome as a foundation for systems analysis of the organelle.
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Alternative splicing often leads to the inclusion or exclusion of mitochondrial targeting sequences, leading to two mature proteins that have identical warheads but are localized to two different places.
“Alternative splicing often leads to the inclusion or exclusion of mitochondrial targeting sequences, leading to two mature proteins that have identical warheads but are localized to two different places 13 .”
From How many human proteoforms are there? (2018) · cites this paper as [13]
The Dual Localization section says alternative splicing can produce two proteins from one gene, one with a mitochondrial targeting sequence, that localize to different compartments. It does not establish that this often happens or that the resulting mature proteins have identical functional regions (“warheads”). Page numbers are not available in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe number of oxidatively-modified mitochondrial proteins characterized may represent a small fraction of the estimated 1100-1400 total mitochondrial proteins.
“The number of oxidatively-modified mitochondrial proteins we characterized may represent a small fraction of the estimated number of 1100–1400 total mitochondrial proteins [40], [41].”
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Cites
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
Self-citationSequence and organization of the human mitochondrial genome
Anderson, S., Bankier, A. T., Barrell, B. G., de Bruijn, M. H. L., Coulson, A. R., Drouin, J., Eperon, I. C., Nierlich, D. P., Roe, B. A., Sanger, F., et al. (1981) · Nature · doi:10.1038/290457a0 · Cited by 9,640 · see citing works
<i>IDH1</i> and <i>IDH2</i> Mutations in Gliomas
Yan, H., Parsons, D. W., Jin, G., McLendon, R., Rasheed, B. A., Yuan, W., Kos, I., Batinic-Haberle, I., Jones, S., Riggins, G. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808710 · Cited by 5,847 · see citing works
Exploring the metabolic and genetic control of gene expression on a genomic scale.
Derisi, J., Iyer, V., & Brown, P. (1997) · Science · doi:10.1126/science.278.5338.680 · Cited by 4,832 · see citing works
Predicting subcellular localization of proteins based on their N-terminal amino acid sequence.
Emanuelsson, O., Nielsen, H., Brunak, S., & von Heijne, G. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3903 · Cited by 4,419 · see citing works
Global analysis of protein localization in budding yeast
Huh, W.-K., Falvo, J. V., Gerke, L. C., Carroll, A. S., Howson, R. W., Weissman, J. S., & O'Shea, E. K. (2003) · Nature · doi:10.1038/nature02026 · Cited by 4,248 · cited 1× · see citing works
“Tagging of endogenous proteins, which has been applied successfully to the yeast proteome (46, 57), has been extended to mouse but is not yet a high-throughput method (83).”
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154 · see citing works
Luo, X., Budihardjo, I., Zou, H., Slaughter, C., & Wang, X. (1998) · Cell · doi:10.1016/s0092-8674(00)81589-5 · Cited by 3,626 · see citing works
tRNA punctuation model of RNA processing in human mitochondria
Ojala, D., Montoya, J., & Attardi, G. M. (1981) · Nature · doi:10.1038/290470a0 · Cited by 2,536 · see citing works
STRING 8--a global view on proteins and their functional interactions in 630 organisms
Jensen, L. J., Kuhn, M., Stark, M., Chaffron, S., Creevey, C. J., Muller, J., Doerks, T., Julien, P., Roth, A. C., Simonovic, M., et al. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn760 · Cited by 2,475 · see citing works
Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy
Wallace, D. C., Singh, G., Lott, M. T., Hodge, J. A., Schurr, T. G., Lezza, A. M. S., Elsas, L. J., & Nikoskelainen, E. K. (1988) · Science · doi:10.1126/science.3201231 · Cited by 2,440 · see citing works
Nakai, K., & Horton, P. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01336-x · Cited by 2,181 · cited 1× · see citing works
“These include TargetP (31), pTARGET (41), PSORT (77), iPSORT (9), Predotar (97), ngLoc (52), MitPred (59), MitoPred (42), and MitoProt (21), as described in a recent comparative review (40).”
A Mitochondrial Protein Compendium Elucidates Complex I Disease Biology
Pagliarini, D. J., Calvo, S. E., Chang, B., Sheth, S. A., Vafai, S. B., Ong, S.-E., Walford, G. A., Sugiana, C., Boneh, A., Chen, W. K., et al. (2008) · Cell · doi:10.1016/j.cell.2008.06.016 · Cited by 1,994 · see citing works
Self-citationExome sequencing identifies the cause of a mendelian disorder
Ng, S. B., Buckingham, K. J., Lee, C., Bigham, A. W., Tabor, H. K., Dent, K. M., Huff, C. D., Shannon, P. T., Jabs, E. W., Nickerson, D. A., et al. (2010) · Nature Genetics · doi:10.1038/ng.499 · Cited by 1,957 · see citing works
Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies
Holt, I. J., Harding, A. E., & MORGAN-HUGHES, J. A. (1988) · Nature · doi:10.1038/331717a0 · Cited by 1,845 · see citing works
p53 Has a Direct Apoptogenic Role at the Mitochondria
Mihara, M., Erster, S. H., Zaika, A. I., Petrenko, O., Chittenden, T. D., Pančoška, P., & Moll, U. M. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00050-9 · Cited by 1,771 · see citing works
Computational method to predict mitochondrially imported proteins and their targeting sequences.
Claros, M. G., & Vincens, P. (1996) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1996.00779.x · Cited by 1,736 · see citing works
The genome sequence of Rickettsia prowazekii and the origin of mitochondria
Andersson, S. G. E., Zomorodipour, A., Andersson, J. O., Sicheritz-Pontén, T., Alsmark, U. C. M., Podowski, R. M., Näslund, A. K., Eriksson, A.-S., Winkler, H. H., & Kurland, C. G. (1998) · Nature · doi:10.1038/24094 · Cited by 1,697 · see citing works
Super-resolution fluorescence microscopy
Huang, B., Bates, M., & Zhuang, X. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.77.061906.092014 · Cited by 1,657 · see citing works
Mitochondrial Respiratory-Chain Diseases
DiMauro, S., & Schon, E. A. (2003) · New England Journal of Medicine · doi:10.1056/nejmra022567 · Cited by 1,650 · see citing works
Assigning protein functions by comparative genome analysis: Protein phylogenetic profiles
Pellegrini, M. A., Marcotte, E. M., Thompson, M. J., Eisenberg, D. S., & Yeates, T. O. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.8.4285 · Cited by 1,568 · see citing works
Large-scale analysis of the human and mouse transcriptomes
Su, A. I., Cooke, M. P., Ching, K. A., Hakak, Y., Walker, J. R., Wiltshire, T., Orth, A. P., Vega, R. G., Sapinoso, L. M., Moqrich, A., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012025199 · Cited by 1,466 · see citing works
Importing Mitochondrial Proteins: Machineries and Mechanisms
Chacińska, A., Koehler, C., Milenkovic, D., Lithgow, T., & Pfanner, N. (2009) · Cell · doi:10.1016/j.cell.2009.08.005 · Cited by 1,446 · see citing works
An ER-Mitochondria Tethering Complex Revealed by a Synthetic Biology Screen
Kornmann, B., Currie, E., Collins, S. R., Schuldiner, M., Nunnari, J., Weissman, J. S., & Walter, P. (2009) · Science · doi:10.1126/science.1175088 · Cited by 1,275 · see citing works
Analysis of the IDH1 codon 132 mutation in brain tumors
Balss, J., Meyer, J., Mueller, W., Korshunov, A., Hartmann, C., & von Deimling, A. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0455-2 · Cited by 1,036 · see citing works
Predotar: A tool for rapidly screening proteomes for N‐terminal targeting sequences
Small, I., Peeters, N., Legeai, F., & Lurin, C. (2004) · Proteomics · doi:10.1002/pmic.200300776 · Cited by 913 · see citing works
A combined algorithm for genome-wide prediction of protein function
Marcotte, E. M., Pellegrini, M. A., Thompson, M. J., Yeates, T. O., & Eisenberg, D. S. (1999) · Nature · doi:10.1038/47048 · Cited by 901 · see citing works
Mootha, V. K., Bunkenborg, J., Olsen, J. V., Hjerrild, M., Wisniewski, J. R., Stahl, E., Bolouri, M. S., Ray, H. N., Sihag, S., Kamal, M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00926-7 · Cited by 889 · see citing works
Self-citationExtensive feature detection of N-terminal protein sorting signals
Bannai, H., Tamada, Y., Maruyama, O., Nakai, K., & Miyano, S. (2002) · Bioinform. · doi:10.1093/bioinformatics/18.2.298 · Cited by 746 · see citing works
Subcellular localization of the yeast proteomePreprint
Kumar, A., Agarwal, S., Heyman, J. A., Matson, S., Heidtman, M. I., Piccirillo, S., Umansky, L., Drawid, A., Jansen, R., Liu, Y., et al. (2002) · Genes & Development · doi:10.1101/gad.970902 · Cited by 737 · see citing works
Characterization of the human heart mitochondrial proteome
Taylor, S. W., Fahy, E., Zhang, B., Glenn, G. M., Warnock, D. E., Wiley, S. E., Murphy, A. N., Gaucher, S. P., Capaldi, R., Gibson, B. W., et al. (2003) · Nature Biotechnology · doi:10.1038/nbt793 · Cited by 702 · see citing works
Mootha, V. K., Handschin, C., Arlow, D., Xie, X., St. Pierre, J., Sihag, S., Yang, W., Altshuler, D., Puigserver, P., Patterson, N., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401401101 · Cited by 688 · see citing works
Self-citationAn enhanced MITOMAP with a global mtDNA mutational phylogeny
Ruiz‐Pesini, E., Lott, M. T., Procaccio, V., Poole, J. C., Brandon, M., Mishmar, D., Yi, C., Kreuziger, J., Baldi, P., & Wallace, D. C. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl927 · Cited by 644 · see citing works
Distinguishing protein-coding and noncoding genes in the human genome
Clamp, M., Fry, B., Kamal, M., Xie, X., Cuff, J., Lin, M. F., Kellis, M., Lindblad-Toh, K., & Lander, E. S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709013104 · Cited by 624 · see citing works
Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics
Mootha, V. K., Lepage, P., Miller, K., Bunkenborg, J., Reich, M. M., Hjerrild, M., DelMonte, T. A., Villeneuve, A., SLADEK, R. M., Xu, F., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.242716699 · Cited by 578 · see citing works
Self-citationDiagnostic criteria for respiratory chain disorders in adults and children
Bernier, F. P., Boneh, A., Dennett, X., Chow, C. W., Cleary, M., & Thorburn, D. R. (2002) · Neurology · doi:10.1212/01.wnl.0000033795.17156.00 · Cited by 574 · see citing works
A Mammalian Organelle Map by Protein Correlation Profiling
Foster, L. J., de Hoog, C. L., Zhang, Y., Zhang, Y., Xie, X. S., Mootha, V. K., & Mann, M. (2006) · Cell · doi:10.1016/j.cell.2006.03.022 · Cited by 573 · see citing works
Self-citationSystematic screen for human disease genes in yeast
Steinmetz, L. M., Scharfe, C., Deutschbauer, A. M., Mokranjac, D., Herman, Z. S., Jones, T., Chu, A. M., Giaever, G. N., Prokisch, H., Oefner, P. J., et al. (2002) · Nature Genetics · doi:10.1038/ng929 · Cited by 544 · see citing works
Wallace, D. C., Zheng, X., Lott, M. T., Shoffner, J. M., Hodge, J. A., Kelley, R. I., Epstein, C. M., & Hopkins, L. C. (1988) · Cell · doi:10.1016/0092-8674(88)90218-8 · Cited by 537 · see citing works
Kislinger, T., Cox, B., Kannan, A., Chung, C., Hu, P., Ignatchenko, A., Scott, M. S., Gramolini, A. O., Morris, Q., Hallett, M. T., et al. (2006) · Cell · doi:10.1016/j.cell.2006.01.044 · Cited by 482 · see citing works
Genetic Basis of Mitochondrial Function and Morphology in Saccharomyces cerevisiae
Dimmer, K. S., Fritz, S., Fuchs, F., Messerschmitt, M., Weinbach, N., Neupert, W., & Westermann, B. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-12-0588 · Cited by 443 · see citing works
Inherited mitochondrial optic neuropathies
Yu‐Wai‐Man, P., Griffiths, P. G., Hudson, G., & Chinnery, P. F. (2008) · Journal of Medical Genetics · doi:10.1136/jmg.2007.054270 · Cited by 434 · see citing works
Spinazzola, A., Viscomi, C., Fernandez-Vizarra, E., Carrara, F., D'Adamo, P., Calvo, S., Marsano, R. M., Donnini, C., Weiher, H., Strisciuglio, P., et al. (2006) · Nature Genetics · doi:10.1038/ng1765 · Cited by 427 · see citing works
Self-citationThe Layered Structure of Human Mitochondrial DNA Nucleoids
Bogenhagen, D. F., Rousseau, D. L., & Burke, S. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m708444200 · Cited by 426 · see citing works
Tiranti, V., Viscomi, C. F., Hildebrandt, T. M., Meo, I. D., Mineri, R., Tiveron, C., Levitt, M. D., Prelle, A. C., Fagiolari, G., Rimoldi, M., et al. (2009) · Nature Medicine · doi:10.1038/nm.1907 · Cited by 404 · see citing works
Automated protein function prediction--the genomic challenge
Friedberg, I. (2006) · Briefings in Bioinformatics · doi:10.1093/bib/bbl004 · Cited by 366 · see citing works
DiMauro, S., & Davidzon, G. (2005) · Annals of Medicine · doi:10.1080/07853890510007368 · Cited by 362 · see citing works
Distinctive features of the 5′-terminal sequences of the human mitochondrial mRNAs
Montoya, J., Ojala, D., & Attardi, G. M. (1981) · Nature · doi:10.1038/290465a0 · Cited by 360 · see citing works
Fonseca, S. G., Fukuma, M., Lipson, K. L., Nguyen, L. X., Allen, J. R., Oka, Y., & Urano, F. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507426200 · Cited by 358 · see citing works
Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2
Zuchner, S. L., Jonghe, P. D., Jordanova, A., Claeys, K. G., Guergueltcheva, V., Cherninkova, S., Hamilton, S. R., Stavern, G. P. V., Krajewski, K. M., Stajich, J. M., et al. (2006) · Annals of Neurology · doi:10.1002/ana.20797 · Cited by 357 · see citing works
mtDB: Human Mitochondrial Genome Database, a resource for population genetics and medical sciences
Ingman, M. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj010 · Cited by 357 · see citing works
Systematic identification of human mitochondrial disease genes through integrative genomics
Calvo, S. E., Jain, M., Xie, X. S., Sheth, S. A., Chang, B., Goldberger, O., Spinazzola, A., Zeviani, M., Carr, S. A., & Mootha, V. K. (2006) · Nature Genetics · doi:10.1038/ng1776 · Cited by 344 · see citing works
Self-citationWeraarpachai, W., Antonická, H., Sasarman, F., Seeger, J., Schrank, B., Kolesar, J. E., Lochmüller, H., Chevrette, M., Kaufman, B. A., Horváth, R., et al. (2009) · Nature Genetics · doi:10.1038/ng.390 · Cited by 309 · see citing works
Quantitative Proteomic Comparison of Rat Mitochondria from Muscle, Heart, and Liver *S
Forner, F., Foster, L., Campanaro, S., Valle, G., & Mann, M. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500298-mcp200 · Cited by 289 · see citing works
Ogilvie, I. M. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26020 · Cited by 279 · see citing works
Clinical and molecular findings in children with complex I deficiency
Bugiani, M., Invernizzi, F., Alberio, S., Briem, E., Lamantea, E., Carrara, F., Moroni, I., Farina, L., Spada, M., Donati, M. A., et al. (2004) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2004.09.006 · Cited by 264 · see citing works
MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria
Banci, L., Bertini, I., Cefaro, C., Ciofi‐Baffoni, S., Gallo, A., Martinelli, M., Sideris, D. P., Katrakili, N., & Tokatlidis, K. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1553 · Cited by 260 · see citing works
Wiedemann, N., Pfanner, N., & Ryan, M. T. (2001) · The EMBO Journal · doi:10.1093/emboj/20.5.951 · Cited by 256 · see citing works
Mutations in PYCR1 cause cutis laxa with progeroid features
Reversade, B., Escande‐Beillard, N., Dimopoulou, A., Fischer‐Zirnsak, B., Chng, S. C., Li, Y., Shboul, M., Tham, P.-Y., Kayserili, H., Al‐Gazali, L., et al. (2009) · Nature Genetics · doi:10.1038/ng.413 · Cited by 256 · see citing works
Proteomic analysis of the mouse liver mitochondrial inner membrane
Da Cruz, S., Xenarios, I., Langridge, J., Vilbois, F., Parone, P. A., & Martinou, J.-C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304940200 · Cited by 247 · see citing works
Proteome Differences between Brown and White Fat Mitochondria Reveal Specialized Metabolic Functions
Forner, F., Kumar, C., Luber, C. A., Fromme, T., Klingenspor, M., & Mann, M. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.014 · Cited by 236 · see citing works
Vieira, H. L. A., Haouzi, D., Hamel, C. E., Jacotot, E. D., Belzacq, A.-S., Brenner, C., & Kroemer, G. (2000) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400778 · Cited by 229 · see citing works
Gabaldón, T., Rainey, D. Y., & Huynen, M. A. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.02.067 · Cited by 224 · see citing works
Discovery of Genes Essential for Heme Biosynthesis through Large-Scale Gene Expression Analysis
Nilsson, R., Schultz, I. J., Pierce, E. L., Soltis, K. A., Naranuntarat, A., Ward, D. M., Baughman, J. M., Paradkar, P. N., Kingsley, P. D., Culotta, V., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.06.012 · Cited by 213 · see citing works
Self-citationTissue heterogeneity of the mammalian mitochondrial proteome
Johnson, D., Harris, R. A., French, S. A., Blair, P. V., You, J., Bemis, K. G., Wang, M., & Balaban, R. S. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00108.2006 · Cited by 209 · see citing works
Tiranti, V., D’Adamo, P., Briem, E., et al. (2004) · The American Journal of Human Genetics · doi:10.1086/381653 · Cited by 205 · see citing works
Vrbacká-Čížková, A., Stránecký, V., Mayr, J. A., et al. (2008) · Nature Genetics · doi:10.1038/ng.246 · Cited by 202 · see citing works
Rabilloud, T., Kieffer‐Jaquinod, S., Procaccio, V., Louwagie, M., Courchesne, P. L., Patterson, S. D., Martinez, P., Garin, J., & Lunardi, J. (1998) · Electrophoresis · doi:10.1002/elps.1150190616 · Cited by 197 · see citing works
Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells
Tong, W., & Rouault, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5692 · Cited by 194 · see citing works
Mutation of C20orf7 Disrupts Complex I Assembly and Causes Lethal Neonatal Mitochondrial Disease
Sugiana, C., Pagliarini, D. J., McKenzie, M., Kirby, D. M., Salemi, R., Abu‐Amero, K. K., Dahl, H. M., Hutchison, W. M., Vascotto, K. A., Smith, S. M., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.09.009 · Cited by 178 · see citing works
Self-citationAssigning pathogenicity to mitochondrial tRNA mutations: when ‘definitely maybe’ is not good enough
McFarland, R., Elson, J. L., Taylor, R. W., et al. (2004) · Trends in Genetics · doi:10.1016/j.tig.2004.09.014 · Cited by 176 · see citing works
MitoProteome: mitochondrial protein sequence database and annotation system
Cotter, D. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh048 · Cited by 175 · see citing works
Mitochondrial Fatty Acid Synthesis Type II: More than Just Fatty Acids
Hiltunen, J. K., Schonauer, M. S., Autio, K. J., Mittelmeier, T. M., Kastaniotis, A. J., & Dieckmann, C. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.r800068200 · Cited by 174 · see citing works
Identification of the Signal Directing Tim9 and Tim10 into the Intermembrane Space of Mitochondria
Milenkovic, D., Ramming, T., Müller, J. M., Wenz, L.-S., Gebert, N., Schulze‐Specking, A., Stojanovski, D., Rospert, S., & Chacińska, A. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-11-1108 · Cited by 167 · see citing works
Hydroxyglutaric aciduria and malignant brain tumor: a case report and literature review
Aghili, M., Zahedi, F., & Rafiee, E. (2009) · Journal of Neuro-Oncology · doi:10.1007/s11060-008-9706-2 · Cited by 159 · see citing works
OPA3 gene mutations responsible for autosomal dominant optic atrophy and cataract
Reynier, P., Amati‐Bonneau, P., Verny, C., Olichon, A., Simard, G., Guichet, A., Bonnemains, C., Malecaze, F., Malinge, M. C., Pelletier, J. B., et al. (2004) · Journal of Medical Genetics · doi:10.1136/jmg.2003.016576 · Cited by 159 · see citing works
Baughman, J. M., Nilsson, R., Gohil, V. M., Arlow, D. H., Gauhar, Z., & Mootha, V. K. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000590 · Cited by 156 · see citing works
Self-citationVo, T. D., Greenberg, H. J., & Palsson, B. Ø. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403782200 · Cited by 154 · see citing works
Hydrogenosomes, Mitochondria and Early Eukaryotic Evolution
Embley, T. M., van der Giezen, M., Horner, D. S., Dyal, P. L., Bell, S., & Foster, P. G. (2003) · IUBMB Life · doi:10.1080/15216540310001592834 · Cited by 152 · see citing works
MITOPRED: a genome-scale method for prediction of nucleus-encoded mitochondrial proteins
Guda, C., Fahy, E., & Subramaniam, S. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth171 · Cited by 136 · see citing works
Transcriptional responses to intermittent hypoxia
Nanduri, J., Yuan, G., Kumar, G. K., Semenza, G. L., & Prabhakar, N. R. (2008) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2008.07.006 · Cited by 130 · see citing works
Sequence variation in mitochondrial complex I genes: mutation or polymorphism?
Mitchell, A. L., Elson, J. L., Howell, N., et al. (2005) · Journal of Medical Genetics · doi:10.1136/jmg.2005.032474 · Cited by 126 · see citing works
A genetic approach to identifying mitochondrial proteins
Ozawa, T., Sako, Y., Sato, M., et al. (2003) · Nature Biotechnology · doi:10.1038/nbt791 · Cited by 125 · see citing works
Gabaldón, T., & Huynen, M. A. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030219 · Cited by 123 · see citing works
Prediction of Mitochondrial Proteins Using Support Vector Machine and Hidden Markov Model
Kumar, M., Verma, R., & Raghava, G. P. S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m511061200 · Cited by 114 · see citing works
In-depth Analysis of the Adipocyte Proteome by Mass Spectrometry and Bioinformatics
Adachi, J., Kumar, C., Zhang, Y., & Mann, M. (2007) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m600476-mcp200 · Cited by 112 · see citing works
Functional consequences of mitochondrial proteome heterogeneity
Johnson, D., Harris, R. A., Blair, P. V., & Balaban, R. S. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00109.2006 · Cited by 109 · see citing works
ngLOC: an n-gram-based Bayesian method for estimating the subcellular proteomes of eukaryotes
King, B. R., & Guda, C. (2007) · Genome biology · doi:10.1186/gb-2007-8-5-r68 · Cited by 102 · see citing works
Boja, E. S., Phillips, D. J., French, S. A., Harris, R. A., & Balaban, R. S. (2009) · Journal of Proteome Research · doi:10.1021/pr900387b · Cited by 100 · see citing works
Molecular genetics of human aldehyde dehydrogenase
Yoshida, A. (1992) · Pharmacogenetics · doi:10.1097/00008571-199208000-00001 · Cited by 96 · see citing works
Mapping Gene Associations in Human Mitochondria using Clinical Disease Phenotypes
Scharfe, C., Lu, H. H., Neuenburg, J. K., Allen, E. A., Li, G.-C., Klopstock, T., Cowan, T. M., Enns, G. M., & Davis, R. W. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000374 · Cited by 85 · see citing works
Assessing Systems Properties of Yeast Mitochondria through an Interaction Map of the Organelle
Perocchi, F., Jensen, L. J., Gagneur, J., Ahting, U., von Mering, C., Peer Bork, B., Prokisch, H., & Steinmetz, L. M. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020170 · Cited by 76 · see citing works
MitoMiner, an Integrated Database for the Storage and Analysis of Mitochondrial Proteomics Data
Smith, A. C., & Robinson, A. J. (2009) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m800373-mcp200 · Cited by 76 · see citing works
MitoP2: An Integrative Tool for the Analysis of the Mitochondrial Proteome
Elstner, M., Andréoli, C., Ahting, U., Tetko, I. V., Klopstock, T., Meitinger, T., & Prokisch, H. (2008) · Molecular Biotechnology · doi:10.1007/s12033-008-9100-5 · Cited by 70 · see citing works
Goethem, G. V., Löfgren, A., Dermaut, B., Ceuterick, C., Martin, J., & Broeckhoven, C. V. (2003) · Human Mutation · doi:10.1002/humu.10246 · Cited by 65 · see citing works
Complexity and tissue specificity of the mitochondrial respiratory chain
Capaldi, R. A., González‐Halphen, D., Zhang, Y., & Yanamura, W. (1988) · Journal of Bioenergetics and Biomembranes · doi:10.1007/bf00769634 · Cited by 64 · see citing works
pTARGET: a web server for predicting protein subcellular localization
Guda, C. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl093 · Cited by 62 · see citing works
Uusimaa, J., Finnilä, S., Remes, A. M., et al. (2004) · PEDIATRICS · doi:10.1542/peds.114.2.443 · Cited by 58 · see citing works
20 years of human mtDNA pathologic point mutations: Carefully reading the pathogenicity criteria
Montoya, J., López‐Gallardo, E., Díez‐Sánchez, C., López-Pérez, M. J., & Ruiz‐Pesini, E. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.09.003 · Cited by 58 · see citing works
Schuler, A. M., Gower, B. A., Matern, D., et al. (2005) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2004.09.006 · Cited by 57 · see citing works
Tranebjærg, L., Jensen, P. K. A., Ghelue, M. V., Vnencak‐Jones, C. L., Sund, S., Elgjo, K. M., Jakobsen, J., Lindal, S., Warburg, M., Fuglsang‐Frederiksen, A., et al. (2001) · Ophthalmic Genetics · doi:10.1076/opge.22.4.207.2220 · Cited by 55 · see citing works
Approaches to Finding the Molecular Basis of Mitochondrial Oxidative Phosphorylation Disorders
Kirby, D. M., & Thorburn, D. R. (2008) · Twin Research and Human Genetics · doi:10.1375/twin.11.4.395 · Cited by 55 · see citing works
Aponte, A. M., Phillips, D. J., Harris, R. A., Blinova, K., French, S. A., Johnson, D., & Balaban, R. S. (2009) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(09)05004-6 · Cited by 52 · see citing works
Evolution of mitochondrial protein biogenesis
Kutik, S., Stroud, D. A., Wiedemann, N., & Pfanner, N. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.04.004 · Cited by 46 · see citing works
Searching for nuclear-mitochondrial genes
Chinnery, P. F. (2003) · Trends in Genetics · doi:10.1016/s0168-9525(02)00030-6 · Cited by 45 · see citing works
Regulators of membrane trafficking andMycobacterium tuberculosis phagosome maturation block
Fratti, R. A., Vergne, I., Chua, J., Skidmore, J. M., & Deretic, V. P. (2000) · Electrophoresis · doi:10.1002/1522-2683(20001001)21:16 · Cited by 43 · see citing works
Vockley, J. E. (2008) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-008-1005-8 · Cited by 43 · see citing works
Scheffler, N. K., Miller, S. W., Carroll, A. K., Anderson, C. M., Davis, R. E., Ghosh, S. S., & Gibson, B. W. (2001) · Mitochondrion · doi:10.1016/s1567-7249(01)00007-1 · Cited by 43 · see citing works
Palmfeldt, J., Vang, S., Stenbroen, V., Pedersen, C. B., Christensen, J., Bross, P., & Gregersen, N. (2009) · Proteome Science · doi:10.1186/1477-5956-7-20 · Cited by 42 · see citing works
Use of 32P To Study Dynamics of the Mitochondrial Phosphoproteome
Aponte, A. M., Phillips, D. J., Hopper, R. K., Johnson, D., Harris, R. A., Blinova, K., Boja, E. S., French, S. A., & Balaban, R. S. (2009) · Journal of Proteome Research · doi:10.1021/pr800913j · Cited by 42 · see citing works
Kölker, S., Mayatepek, E., & Hoffmann, G. F. (2002) · Neuropediatrics · doi:10.1055/s-2002-36741 · Cited by 39 · see citing works
Pathogenic mutations of nuclear genes associated with mitochondrial disorders
Zhu, X., Peng, X.-R., Guan, M., & Yan, Q. (2009) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmn021 · Cited by 39 · see citing works
Post-translational modification of proteins during intermittent hypoxia
Kumar, G., & Prabhakar, N. R. (2008) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2008.05.017 · Cited by 38 · see citing works
Mehrle, A. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj139 · Cited by 38 · see citing works
Mitochondrial proteome evolution and genetic disease
Huynen, M. A., de Hollander, M., & Szklarczyk, R. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.03.005 · Cited by 31 · see citing works
Gaston, D., Tsaousis, A. D., & Roger, A. J. (2009) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(09)05002-2 · Cited by 28 · see citing works
Catastrophic presentation of mitochondrial disease due to a mutation in the tRNA His gene
Taylor, R. W., Schaefer, A. M., McDonnell, M. T., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000120667.77372.46 · Cited by 25 · see citing works
Mitochondrial myopathy associated with a novel mutation in mtDNA
Pancrudo, J., Shanske, S., Çoku, J., et al. (2007) · Neuromuscular Disorders · doi:10.1016/j.nmd.2007.04.005 · Cited by 22 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- [63]Marchenko ND Zaika A Moll UM Death signal--induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J. Biol. Chem 2000 275 16202 -12 10821866
- [76]Morava E van den Heuvel L Hol F de Vries MC Hogeveen M Mitochondrial disease criteria: diagnostic applications in children. Neurology 2006 67 1823 -6 17130416
- [104]Thiele I Price ND Vo TD Palsson BO Candidate metabolic network states in human mitochondria. Impact of diabetes, ischemia, and diet. J. Biol. Chem 2005 280 11683 -95 15572364
- [109]Tyni T Kivela T Lappi M Summanen P Nikoskelainen E Pihko H Ophthalmologic findings in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency caused by the G1528C mutation: a new type of hereditary metabolic chorioretinopathy. Ophthalmology 1998 105 810 -24 9593380
- [115]Walker UA Collins S Byrne E Respiratory chain encephalomyopathies: a diagnostic classification. Eur. Neurol 1996 36 260 -67 8864705
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Chen, Y., Zhou, Z., & Min, W. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01487 · Cited by 315 · see citing works
Neufeld-Cohen, A., Robles, M. S., Aviram, R., Manella, G., Adamovich, Y., Ladeuix, B., Nir, D., Rousso-Noori, L., Kuperman, Y., Golik, M., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1519650113 · Cited by 262 · see citing works
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Haas, R., Zelezniak, A., Iacovacci, J., Kamrad, S., Townsend, S., & Ralser, M. (2017) · Current Opinion in Systems Biology · doi:10.1016/j.coisb.2017.08.009 · Cited by 131 · see citing works
Song, B.-J., Akbar, M., Abdelmegeed, M. A., Byun, K., Lee, B., Yoon, S. K., & Hardwick, J. P. (2014) · Redox Biology · doi:10.1016/j.redox.2014.10.004 · Cited by 123 · see citing works
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- Authors
- Calvo, S. E., & Mootha, V. K.
- Affiliations
- Broad Institute (US)
- Venue
- Annual Review of Genomics and Human Genetics
- Publisher
- Annual Reviews
- Published
- 2010-09-01
- Volume
- 11
- Issue
- 1
- Pages
- 25-44
- ISSN
- 1527-8204 (ISSN-L)
- 1545-293X
- PMC
- PMC4397899
- OpenAlex
- W2624338235
- Cited by
- 590
- References
- 118
- Citations by year
- 2026: 19 · 2025: 20 · 2024: 31 · 2023: 32 · 2022: 49 · 2021: 61 · 2020: 60 · 2019: 38 · 2018: 41 · 2017: 40 · 2016: 28 · 2015: 39 · 2014: 38 · 2013: 37 · 2012: 35
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Genomics and Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM077465)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- mitochondrial proteome, mitochondrial disease, respiratory chain disorders, maternally inherited disease, mitochondrial genome, tissue heterogeneity, mitochondrial evolution, genetic basis of disease
- MeSH terms
- Cell Nucleus, Humans, Mitochondria, Proteome, Mitochondrial Proteins, Mitochondrial Diseases, Genome, Mitochondrial
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