Mitochondrial Translation in Health and Disease


Mitochondrial disorders have become the most common cause of inborn errors of metabolism. Impairments in mitochondrial protein synthesis are one of the causes of these diseases, which are clinically and genetically heterogeneous. The mitochondrial translation machinery decodes 13 polypeptides essential for the oxidative phosphorylation process. Mitochondria protein synthesis depends on the integrity of mitochondrial rRNAs and tRNAs genes, and at least one hundred of nuclear encoded products. Diseases caused by mutations in mitochondrial genes as well as in ribosomal proteins, translational factors, RNA modifying enzymes, and all other constituents of the translational machinery have been described in patients with combine respiratory chain deficiency, and are the object of this review.

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C. Ferreiro-Barros and M. Barros, "Mitochondrial Translation in Health and Disease," Open Journal of Endocrine and Metabolic Diseases, Vol. 3 No. 2A, 2013, pp. 1-9. doi: 10.4236/ojemd.2013.32A001.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] E. J. Tucker, A. G. Compton, S. E. Calvo and D. R. Thorburn, “The Molecular Basis of Human Complex I Deficiency,” IUBMB Life, Vol. 63, No. 9, 2011, pp. 669-677.
[2] L. M. Cree, D. C. Samuels and P. F. Chinnery, “The Inheritance of Pathogenic Mitochondrial DNA Mutations,” Biochimica et Biophysica Acta, Vol. 1792, No. 12, 2009, pp. 1097-1102. doi:10.1016/j.bbadis.2009.03.002
[3] D. R. Thorburn, “Mitochondrial Disorders: Prevalence, Myths and Advances,” Journal of Inherited Metabolic Disease, Vol. 27, No. 3, 2004, pp. 349-362. doi:10.1023/B:BOLI.0000031098.41409.55
[4] S. Anderson , A. T. Bankier, B. G. Barrell, M. H. de Bruijn, A. R. Coulson, J. Drouin, I. C. Eperon, D. P. Nierlich, B. A. Roe, F. Sanger, P. H. Schreier, A. J. Smith, R. Staden and I. G. Young, “Sequence and Organization of the Human Mitochondrial Genome,” Nature, Vol. 290, No. 5806, 1981, pp. 457-465. doi:10.1038/290457a0
[5] S. DiMauro, E. Bonilla, M. Davidson, M. Hirano and E. A. Schon, “Mitochondria in Neuromuscular Disorders,” Biochimica et Biophysica Acta, Vol. 1366, No. 1-2, 1998, pp. 199-210. doi:10.1016/S0005-2728(98)00113-3
[6] S. DiMauro, E. Bonilla and D. C. De Vivo, “Does the Patient Have a Mitochondrial Encephalomyopathy?” Journal of Child Neurology, Vol. 14, No. 1, 1999, pp. S23-S35.
[7] I. J. Holt, A. E. Harding and J. A. Morgan-Hughes, “Deletions of Muscle Mitochondrial DNA in Patients with Mitochondrial Myopathies,” Nature, Vol. 331, No. 6158, 1988, pp. 717-719. doi:10.1038/331717a0
[8] M. Hirano and T. H. Vu, “Defects of Intergenomic Communication: Where Do We Stand?” Brain Pathology, 2000 Vol. 10, No. 3, 2000, pp. 451-461. doi:10.1111/j.1750-3639.2000.tb00277.x
[9] C. Scharfe, H. H. Lu, J. K. Neuenburg, E. A. Allen, G. C. Li, T. Klopstock, T. M. Cowan, G. M. Enns and R. W. Davis, “Mapping Gene Associations in Human Mitochondria Using Clinical Disease Phenotypes,” PLoS Computational Biology, Vol. 5, 2009, Article ID: e1000374. doi:10.1371/journal.pcbi.1000374
[10] A. Tzagoloff and C. L. Dieckmann, “PET Genes of Saccharomyces Cerevisiae,” Microbiology Review, Vol. 54, No. 3, 1990, pp. 211-225.
[11] M. Falkenberg, N. G. Larsson and C. M. Gustafsson, “DNA Replication and Transcription in Mammalian Mitochondria,” Annual Review of Biochemistry, Vol. 76, 2007, pp. 679-699. doi:10.1146/annurev.biochem.76.060305.152028
[12] D. A. Clayton, “Transcription and Replication of Animal Mitochondrial DNAs,” International Review of Cytology, Vol. 141, 1992, pp. 217-232. doi:10.1016/S0074-7696(08)62067-7
[13] J. M. Herrmann, M. W. Woellhaf and N. Bonnefoy, “Control of Protein Synthesis in Yeast Mitochondria: The Concept of Translational Activators,” Biochimica et Biophysica Acta, Vol. 1833, No. 2, 2013, pp. 286-294. doi:10.1016/j.bbamcr.2012.03.007
[14] R. P. Fisher and D. A. Clayton, “A Transcription Factor Required for Promoter Recognition by Human Mitochondrial RNA Polymerase. Accurate Initiation at the Heavy- and Light-Strand Promoters Dissected and Reconstituted in Vitro,” Journal of Biological Chemistry, Vol. 260, No. 20, 1985, pp. 11330-11338.
[15] M. Falkenberg, M. Gaspari, A. Rantanen, A. Trifunovic, N. G. Larsson and C. M. Gustafsson, “Mitochondrial Transcription Factors B1 and B2 Activate Transcription of Human mtDNA,” Nature Genetics, Vol. 31, No. 3, 2002, pp. 289-294. doi:10.1038/ng909
[16] H. B. Ngo, J. T. Kaiser and D. C. Chan, “The Mitochondrial Transcription and Packaging Factor Tfam Imposes a U-Turn on Mitochondrial DNA,” Nature Structural and Molecular Biology, Vol. 18, No. 11, 2011, pp. 1290-1296. doi:10.1038/nsmb.2159
[17] A. Rubio-Cosials, J. F. Sidow, N. Jiménez-Menéndez, P. Fernández-Millán, J. Montoya, H. T. Jacobs, M. Coll, P. Bernadó and M. Solà, “Human Mitochondrial Transcription Factor A Induces a U-Turn Structure in the Light Strand Promoter,” Nature Structural and Molecular Biology, Vol. 18, No. 11, 2011, pp. 1281-1289. doi:10.1038/nsmb.2160
[18] Y. Shi, A. Dierckx, P. H. Wanrooij, S. Wanrooij, N. G. Larsson, L. M. Wilhelmsson, M. Falkenberg and C. M. Gustafsson, “Mammalian Transcription Factor A is a Core Component of the Mitochondrial Transcription Machinery,” Proceedings of the National Academy of Science of USA, Vol. 109, No. 41, 2012, pp. 16510-16515. doi:10.1073/pnas.1119738109
[19] M. I. Ekstrand, M. Falkenberg, A. Rantanen, C. B. Park, M. Gaspari, K. Hultenby, P. Rustin, C. M. Gustafsson and N. G. Larsson, “Mitochondrial Transcription Factor A Regulates mtDNA Copy Number in Mammals,” Human Molecular Genetics, Vol. 13, No. 9, 2004, pp. 935-944.
[20] C. Kukat, C. A. Wurm, H. Spahr, M. Falkenberg, N. G. Larsson and S. Jakobs, “Super-Resolution Microscopy Reveals that Mammalian Mitochondrial Nucleoids Have a Uniform Size and Frequently Contain a Single Copy of mtDNA,” Proceedings of the National Academy of Science of USA, Vol. 108, No. 33, 2011, pp. 13534-13539. doi:10.1073/pnas.1109263108
[21] D. Ojala, S. Crews, J. Montoya, R. Gelfand and G. Attardi, “A Small Polyadenylated RNA (7 S RNA), Containing a Putative Ribosome Attachment Site, Maps near the Origin of Human Mitochondrial DNA Replication,” Journal of Molecular Biology, Vol. 150, No. 2, 1981, pp. 303-314. doi:10.1016/0022-2836(81)90454-X
[22] T. Nagaike, T. Suzuki, T. Katoh and T. Ueda, “Human Mitochondrial mRNAs Are Stabilized with Polyadenylation Regulated by Mitochondria-Specific Poly(A) Polymerase and Polynucleotide Phosphorylase,” Journal of Biological Chemistry, Vol. 280, No. 20, 2005, pp. 19721-19727. doi:10.1074/jbc.M500804200
[23] M. Wydro, A. Bobrowicz, R. J. Temperley and R. N. Lightowlers, “Chrzanowska-Lightowlers ZM. Targeting of the Cytosolic Poly(A) Binding Protein PABPC1 to Mitochondria Causes Mitochondrial Translation Inhibition,” Nucleic Acids Research, Vol. 38, No. 11, 2010, pp. 3732-3742. doi:10.1093/nar/gkq068
[24] B. E. Christian and L. L. Spremulli, “Mechanism of Protein Biosynthesis in Mammalian Mitochondria,” Biochimica et Biophysica Acta, Vol. 1819, No. 9-10, 2012, pp. 1035-1054. doi:10.1016/j.bbagrm.2011.11.009
[25] J. Montoya, D. Ojala and G. Attardi, “Distinctive Features of the 5’-Terminal Sequences of the Human Mitochondrial mRNAs,” Nature, Vol. 290, No. 5806, 1981, pp. 465-470. doi:10.1038/290465a0
[26] H. X. Liao and L. L. Spremulli, “Identification and Initial Characterization of Translational Initiation Factor 2 from Bovine Mitochondria,” Journal of Biological Chemistry, Vol. 265, No. 23, 1990, pp.13618-13622.
[27] L. Ma and L. L. Spremulli, “Cloning and Sequence Analysis of the Human Mitochondrial Translational Initiation Factor 2 cDNA,” Journal of Biological Chemistry, Vol. 270, No. 4, 1995, pp. 1859-1865. doi:10.1074/jbc.270.4.1859
[28] E. C. Koc and L. L. Spremulli, “RNA-Binding Proteins of Mammalian Mitochondria,” Mitochondrion, Vol. 2, No. 4, 2003, pp. 277-291. doi:10.1016/S1567-7249(03)00005-9
[29] S. G. Bonitz, R. Berlani, G. Coruzzi, M. Li, G. Macino, F. G. Nobrega, M. P. Nobrega, B. E. Thalenfeld and Tzagoloff, “Codon Recognition Rules in Yeast Mitochondria,” Proceedings of the National Academy of Science of USA, Vol. 77, No. 6, 1980, pp. 3167-3170. doi:10.1073/pnas.77.6.3167
[30] E. Vilardo, C. Nachbagauer, A. Buzet, A. Taschner, J. Holzmann and W. A. Rossmanith, “A Subcomplex of Human Mitochondrial RNase P Is a Bifunctional Methyltransferase—Extensive Moonlighting in Mitochondrial tRNA Biogenesis,” Nucleic Acids Research, Vol. 40, No. 22, 2012, pp. 11583-11593. doi:10.1093/nar/gks910
[31] A. Tzagoloff, D. Gatti and A. Gampel, “Mitochondrial Aminoacyl-tRNA Synthetases,” Progress in Nucleic Acid Research and Molecular Biology, Vol. 39, 1990, pp. 129-158. doi:10.1016/S0079-6603(08)60625-X
[32] M. Wilcox and M. Nirenberg, “Transfer RNA as a Cofactor Coupling Amino Acid Synthesis with That of Protein,” Proceedings of the National Academy of Science of USA, Vol. 61, 1968, pp. 229-236. doi:10.1073/pnas.61.1.229
[33] J. Lapointe, L. Duplain and M. Proulx, “A Single Glutamyl-tRNA Synthetase Aminoacylates tRNAGlu and tRN-AGln in Bacillus Subtilis and Efficientlymisacylates Escherichia Coli tRNAGln1 in Vitro,” Journal of Bacteriology, Vol. 165, 1986, pp. 88-93.
[34] C. Pujol, M. Bailly, D. Kern, L. Maréchal-Drouard, H. Becker and A. M. Duchêne, “Dual-Targeted tRNA-Dependent Amidotransferase Ensures Both Mitochondrial Andchloroplastic Gln-tRNAGln Synthesis in Plants,” Proceedings of the National Academy of Science of USA, Vol. 105, No. 17, 2008, pp. 6481-6485. doi:10.1073/pnas.0712299105
[35] M. Frechin, B. Senger, M. Brayé, D. Kern, R. P. Martin and H. D. Becker, “Yeast Mitochondrial Gln-tRNA(Gln) is Generated by a GatFAB-Mediated Transamidation Pathway Involving Arc1p-controlled Subcellular Sorting of Cytosolic GluRS,” Genes and Development, Vol. 23, 2009, pp.1119-1130. doi:10.1101/gad.518109
[36] A. Nagao, T. Suzuki, T. Katoh, Y. Sakaguchi and T. Suzuki, “Biogenesis of Glutaminyl-mt tRNAGln in Human Mitochondria,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 38, 2009, pp. 16209-16214. doi:10.1073/pnas.0907602106
[37] M. H. Barros, M. Rak, J. A. Paulela and A. Tzagoloff. “Characterization of Gtf1p, the Connector Subunit of Yeast Mitochondrial tRNA-Dependent Amidotransferase,” The Journal of Biological Chemistry, Vol. 286, No. 38, 2011, pp. 32937-32947. doi:10.1074/jbc.M111.265371
[38] J. R. Patton, Y. Bykhovskaya, E. Mengesha, C. Bertolotto, N. Fischel-Ghodsian, “Mitochondrial Myopathy and Sideroblastic Anemia (MLASA): Missense Mutation in the Pseudouridine Synthase 1 (PUS1) Gene Is Associated with the Loss of tRNA Pseudouridylation,” The Journal of Biological Chemistry, Vol. 280, No. 20, 2005, pp. 19823-19828. doi:10.1074/jbc.M500216200
[39] X. Wang, Q. Yan and M. X. Guan, “Combination of the Loss of cmnm5U34 with the Lack of s2U34 Modifications of tRNALys, tRNAGlu, and tRNAGln Altered Mitochondrial Biogenesis and Respiration,” The Journal of Biological Chemistry, Vol. 395, No. 5, 2010, pp. 1038-1048. doi:10.1016/j.jmb.2009.12.002
[40] Q. Yan, Y. Bykhovskaya, R. Li, E. Mengesha, M. Shohat, X. Estivill, N. Fischel-Ghodsian and M. X. Guan, “Human TRMU Encoding the Mitochondrial 5-Methylaminomethyl-2-thiouridylate-methyltransferase Is a Putative Nuclear Modifier Gene for the Phenotypic Expression of the Deafness-Associated 12S rRNA Mutations,” Biochemical and Biophysical Research Communications, Vol. 342, No. 4, 2006, pp. 1130-1136. doi:10.1016/j.bbrc.2006.02.078
[41] A. Zeharia, A. Shaag, O. Pappo, A. M. Mager-Heckel, A. Saada, M. Beinat, O. Karicheva, H. Mandel, N. Ofek, R. Segel, D. Marom, A. Rotig, I. Tarassov and O. Elpeleg, “Acuteinfantile Liver Failure Due to Mutations in the TRMU Gene,” The American Journal of Human Genetics, Vol. 85, No. 3, 2009, pp. 401-417. doi:10.1016/j.ajhg.2009.08.004
[42] M. Liu and L. Spremulli, “Interaction of Mammalian Mitochondrial Ribosomes with the Inner Membrane,” The Journal of Biological Chemistry, Vol. 275, No. 38, 2000, pp. 29400-29406. doi:10.1074/jbc.M002173200
[43] A. Tzagoloff, “Genetic and Translational Capabilities of the Mitochondrion,” BioScience, Vol. 27, No. 1, 1977, pp. 18-23. doi:10.2307/1297789
[44] P. Smits, J. A. Smeitink, L. P. van den Heuvel, M. A. Huynen and T. J. Ettema, “Reconstructing the Evolution of the Mitochondrial Ribosomal Proteome,” Nucleic Acids Research, Vol. 35, No. 14, 2007, pp. 4686-4703. doi:10.1093/nar/gkm441
[45] T. W. O’Brien, “Properties of Human Mitochondrial Ribosomes,” IUBMB Life, Vol. 55, No. 9, 2003, pp. 505-513. doi:10.1080/15216540310001626610
[46] E. C. Koc, W. Burkhart, K. Blackburn, A. Moseley, H. Koc and L. L. Spremulli, “A Proteomics Approach to the Identification of Mammalian Mitochondrial Small Subunit Ribosomal Proteins,” The Journal of Biological Chemistry, Vol. 275, No. 42, 2000, pp. 32585-32591. doi:10.1074/jbc.M003596200
[47] E. C. Koc, W. Burkhart, K. Blackburn, M. B. Moyer, D. M. Schlatzer, A. Moseley and L. L. Spremulli, “The Large Subunit of the Mammalian Mitochondrial Ribosome. Analysis of the Complement of Ribosomal Proteins Present,” The Journal of Biological Chemistry, Vol. 276, No. 47, 2001, pp. 43958-43969. doi:10.1074/jbc.M106510200
[48] A. Barrientos, D. Korr, K. J. Barwell, C. Sjulsen, C. D. Gajewski, G. Manfredi, S. Ackerman and A. Tzagoloff, “MTG1 Codes for a Conserved Protein Required for Mitochondrialtranslation,” Molecular Biology of the Cell, Vol. 14, No. 6, 2003, pp. 2292-2302. doi:10.1091/mbc.E02-10-0636
[49] K. Datta, J. L. Fuentes and J. R. Maddock, “The Yeast GTPase Mtg2p Is Required for Mitochondrial Translation and Partially Suppresses an rRNA Methyltransferase Mutant, mrm2,” Molecular Biology of the Cell, Vol. 16, No. 2, 2005, pp. 954-963. doi:10.1091/mbc.E04-07-0622
[50] M. F. Paul, G. M. Alushin, M. H. Barros, M. Rak and A. Tzagoloff, “The Putative GTPase Encoded by MTG3 Functions in a Novel Pathway for Regulating Assembly of the Small Subunit of Yeast Mitochondrial Ribosomes,” The Journal of Biological Chemistry, Vol. 287, No. 29, 2012, pp. 24346-24355. doi:10.1074/jbc.M112.363309
[51] T. Kotani, S. Akabane, K. Takeyasu, T. Ueda and N. Takeuchi, “Human G-Proteins, ObgH1 and Mtg1, Associate with the large Mitochondrial Ribosome Subunit and Are Involved in Translation and Assembly of Respiratory Complexes,” Nucleic Acids Research, Vol. 41, No. 6, 2013, pp. 3713-3722. doi:10.1093/nar/gkt079
[52] J. Rorbach, P. A. Gammage and M. Minczuk, “C7orf30 Is Necessary for Biogenesis of the Large Subunit of the Mitochondrial Ribosome,” Nucleic Acids Research, Vol. 40, No. 9, 2012, pp. 4097-4109. doi:10.1093/nar/gkr1282
[53] S. Dennerlein, A. Rozanska, M. Wydr, Z. M. Chrzanowska-Lightowlers and R. N. Lightowlers, “Human ERAL1 Is a Mitochondrial RNA Chaperone Involved in the Assembly of the 28S Small Mitochondrial Ribosomal Subunit,” Biochemical Journal, Vol. 430, No. 3, 2010, pp. 551-558. doi:10.1042/BJ20100757
[54] J. He , H. M. Cooper, A. Reyes, M. Di Re, L. Kazak, S. R. Wood, C. C. Mao, I. M. Fearnley, J. E. Walker and I. J. Holt, “Human C4orf14 Interacts with the Mitochondrial Nucleoid and Is Involved in the Biogenesis of the Small Mitochondrial Ribosomal Subunit,” Nucleic Acids Research, Vol. 40, No. 13, 2012, pp. 6097-6108. doi:10.1093/nar/gks257
[55] M. C. Costanzo and T. D. Fox, “Control of Mitochondrial Gene Expression in Saccharomyces cerevisiae,” Annual Review of Genetics, Vol. 24, No. 1, 1990, pp. 91-113. doi:10.1146/
[56] M. Stanzel, A. Schon and M. Sprinzl, “Discrimination against Misacylated tRNA by Chloroplast Elongation Factor Tu,” European Journal of Biochemistry, Vol. 219, No. 1-2, 1994, pp. 435-439. doi:10.1111/j.1432-1033.1994.tb19956.x
[57] H. Antonicka, E. Ostergaard, F. Sasarman, W. Weraarpachai, F. Wibrand, A. M. Pedersen, R. J. Rodenburg, M. S. van der Knaap, J. A Smeitink, et al., “Mutations in C12orf65 in Patients with Encephalomyopathy and a Mitochondrial Translation Defect,” The American Journal of Human Genetics, Vol. 87, No. 1, 2010, pp. 115-122. doi:10.1016/j.ajhg.2010.06.004
[58] N. G. Larsson and D. A. Clayton, “Molecular Genetic Aspects of Human Mitochondrial Disorders,” Annual Review of Genetics, Vol. 29, No. 1, 1995, pp. 151-178. doi:10.1146/
[59] A. Rotig, “Human Diseases with Impaired Mitochondrial Protein Synthesis,” Biochimica et Biophysica Acta, Vol. 1807, No. 9, 2011, pp. 1198-1205.
[60] S. Pearce, C. L. Nezich and A. Spinazzola, “Mitochondrial Diseases: Translation Matters,” Molecular and Cellular Neuroscience, Vol. 55, 2012, pp. 1-12.
[61] J. A. Morgan-Hughes and M. G. Hanna, “Mitochondrial Encephalomyopathies: The Enigma of Genotype versus Phenotype,” Biochimica et Biophysica Acta, Vol. 1410, No. 2, 1999, pp. 125-145. doi:10.1016/S0005-2728(98)00162-5
[62] S. W. Schaffer, C. J. Jong, D. Warner, T. Ito and J. Azuma, “Taurine Deficiency and MELAS Are Closely Related Syndromes,” Advances in Experimental Medicine and Biology, Vol. 776, 2013, pp. 153-165. doi:10.1007/978-1-4614-6093-0_16
[63] W. Reardon, “Genetic Deafness,” Journal of Medical Genetics, Vol. 29, No. 8, 1992, pp. 521-526. doi:10.1136/jmg.29.8.521
[64] T. R. Prezant, J. V. Agapian, M. C. Bohlman, X. Bu, S. Oztas, W. Q. Qiu, et al., “Mitochondrial Ribosomal RNA Mutationassociated with Both Antibiotic-Induced and Non-Syndromic Deafness,” Nature Genetics, Vol. 4, No. 3, 1993, pp. 289-294. doi:10.1038/ng0793-289
[65] Y. Bykhovskaya, E. Mengesha, D. Wang, H. Yang, X. Estivill, M. Shohat and N. Fischel-Ghodsian, “Phenotype of Non-Syndromic Deafness Associated with the Mitochondrial A1555G Mutation Is Modulated by Mitochondrial RNA Modifying Enzymes MTO1 and GTPBP3,” Molecular Genetics and Metabolism, Vol. 83, No. 3, 2004, pp. 199-206. doi:10.1016/j.ymgme.2004.07.009
[66] C. Miller, A. Saada, N. Shaul, N. Shabtai, E. Ben-Shalom, A. Shaag, E. Hershkovitz and O. Elpeleg, “Defective Mitochondrial Translation Caused by a Ribosomal Protein (MRPS16) Mutation,” Annals of Neurology, Vol. 56, No. 5, 2004, pp. 734-738. doi:10.1002/ana.20282
[67] A. Saada, A. Shaag, S. Arnon, T. Dolfin, C. Miller, D. Fuchs-Telem, A. Lombes and O. Elpeleg, “Antenatal Mitochondrial Disease Caused by Mitochondrial Ribosomal Protein (MRPS22) Mutation,” Journal of Medical Genetics, Vol. 44, No. 12, 2007, pp. 784-786. doi:10.1136/jmg.2007.053116
[68] C. C. Ferreiro-Barros, C. H. Tengan, M. H. Barros, L. Palenzuela, C. Kanki C. Quinzii, J. Lou, N. El Gharaby, A. Shokr, D. C. De Vivo, S. DiMauro and M. Hirano, “Neonatal Mitochondrial Encephaloneuromyopathy Due to a Defect of Mitochondrial Protein Synthesis,” Journal of the Neurological Sciences, Vol. 275, No. 1, 2008, pp. 128-132. doi:10.1016/j.jns.2008.08.028
[69] B. Garcia-Diaz, M. H. Barros, S. Sanna-Cherchi, V. Emmanuele, H. O. Akman, C. C. Ferreiro-Barros, R. Horvath, S. Tadesse, N. El Gharaby, S. Dimauro, D. C. De Vivo, A. Shokr, M. Hirano and C. M. Quinzii, “Infantile Encephaloneuromyopathy and Defective Mitochondrial Translation Are Due to a Homozygous RMND1 Mutation,” The American Journal of Human Genetics, Vol. 91, No. 4, 2012, pp. 729-736. doi:10.1016/j.ajhg.2012.08.019
[70] A. Janer, H. Antonicka, E. Lalonde, T. Nishimura, F. Sasarman, G. K. Brown, R. M. Brown, J. Majewski and E. A. Shoubridge, “An RMND1 Mutation Causes Encephalopathy Associated with Multiple Oxidative Phosphorylation Complex Deficiencies and a Mitochondrial Translation Defect,” The American Journal of Human Genetics, Vol. 91, No. 4, 2012, pp. 737-743. doi:10.1016/j.ajhg.2012.08.020
[71] S. Edvardson, A. Shaag, O. Kolesnikova, J. M. Gomori, I. Tarassov, T. Einbinder, A. Saada and O. Elpeleg, “Deleterious Mutation in the Mitochondrial Arginyl-Transfer RNA Synthetase Gene Is Associated with Pontocerebellar hypoplasia,” The American Journal of Human Genetics, Vol. 81, No. 4, 2007, pp. 857-862. doi:10.1086/521227
[72] S. Yamashita, N. Miyake, N. Matsumoto, H. Osaka, M. Iai, N. Aida and Y. Tanaka, “Neuropathology of Leukoencephalopathy with Brainstem and Spinal Cord Involvement and High Lactate Caused by a Homozygous Mutation of DARS2,” Brain & Development, Vol. 35, No. 4, 2012, pp. 312-316.
[73] R. Belostotsky, E. Ben-Shalom, C. Rinat, R. Becker-Cohen, S. Feinstein, S. Zeligson, R. Segel, O. Elpeleg, S. Nassar and Y. Frishberg, “Mutations in the Mitochondrial seryl-tRNA Synthetase Cause Hyperuricemia, Pulmonary Hypertension, Renal Failure in Infancy and Alkalosis, HUPRA Syndrome,” The American Journal of Human Genetics, Vol. 88, No. 2, 2011, pp. 193-200. doi:10.1016/j.ajhg.2010.12.010
[74] L. G. Riley, S. Cooper, P. Hickey, J. Rudinger-Thirion, M. McKenzie, A. Compton, S. C. Lim, D. Thorburn, M. T. Ryan, R. Giegé, M. Bahlo and J. Christodoulou, “Mutation of the Mitochondrial Tyrosyl-tRNA Synthetase Gene, YARS2, Causes Myopathy, Lactic Acidosis, and Sideroblastic Anemia—MLASA syndrome,” The American Journal of Human Genetics, Vol. 87, No. 1, 2010, pp. 52-59. doi:10.1016/j.ajhg.2010.06.001
[75] S. B. Pierce, K. M. Chisholm, E. D. Lynch, M. K. Lee, T. Walsh, J. M. Opitz, W. Li, R. E Klevit and M.-C. King, “Mutations in Mitochondrial Histidyl tRNA Synthetase HARS2 Cause Ovarian Dysgenesis and Sensorineural Hearing Loss of Perrault Syndrome,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 16, 2011, pp. 6543-6548. doi:10.1073/pnas.1103471108
[76] A, Antonellis and E. D. Green, “The Role of Aminoacyl-tRNA Synthetases in Genetic Diseases,” The American Journal of Human Genetics, Vol. 9, 2008, pp. 87-107. doi:10.1146/annurev.genom.9.081307.164204
[77] W. Weraarpachai, H. Antonicka, F. Sasarman, J. Seeger, B. Schrank, J. E. Kolesar, H. Lochmuller, M. Chevrette, B. A. Kaufman, et al., “Mutation in TACO1, Encoding a Translational Activator of COX I, Results in Cytochrome c Oxidase Deficiency and Late-Onset Leigh Syndrome,” Nature Genetics, Vol. 41, No. 7, 2009, pp. 833-837. doi:10.1038/ng.390
[78] F. Xu, C. Morin, G. Mitchell, C. Ackerley and B. H. Robinson, “The Role of the LRPPRC (Leucine-Rich Pentatricopeptide Repeat Cassette) Gene in Cytochrome Oxidase Assembly: Mutation Causes Lowered Levels of COX (Cytochrome c Oxidase) I and COX III mRNA,” Biochemical Journal, Vol. 382, Pt. 1, 2004, pp. 331-336.
[79] M. J. Coenen, H. Antonicka, C. Ugalde, F. Sasarman, R. Rossi, J. G. Heister, R. F. Newbold, F. J. Trijbels, L. P. van den Heuvel, E. A. Shoubridge and J. A. Smeitink, “Mutant Mitochondrial Elongation Factor G1 and Combined Oxidative Phosphorylation Deficiency,” The New England Journal of Medicine, Vol. 351, No. 20, 2004, pp. 2080-2086. doi:10.1056/NEJMoa041878
[80] J. A. Smeitink, O. Elpeleg, H. Antonicka, H. Diepstra, A. Saada, P. Smits, et al., “Distinct Clinical Phenotypes Associated with a Mutation in the Mitochondrial Translation Elongation Factor EFTs,” The American Journal of Human Genetics, Vol. 79, No. 5, 2006, pp. 869-877. doi:10.1086/508434
[81] I. Valente, V. Tiranti, R. M. Marsano, E. Malfatti, E. Fernandez-Vizarra, C. Donnini, et al., “Infantile Encephalopathy and Defective Mitochondrial DNA Translation in Patients with Mutations of Mitochondrial Elongation Factors EFG1 and EFTu,” The American Journal of Human Genetics, Vol. 80, No. 1, 2007, pp. 44-58. doi:10.1086/510559
[82] H. Antonicka, F. Sasarman, N. G. Kennaway and E. A. Shoubridge, “The Molecular Basis for Tissue Specificity of the Oxidative Phosphorylation Deficiencies in Patients with Mutations in the Mitochondrial Translation Factor EFG1,” Human Molecular Genetics, Vol. 15, No. 11, 2006, pp. 1835-1846. doi:10.1093/hmg/ddl106
[83] P. Smits, H. Antonicka, P. M. van Hasselt, W. Weraarpachai, W. Haller, M. Schreurs, H. Venselaar, R. J. Rodenburg, J. A. Smeitink and L. P. van den Heuvel, “Mutation in Subdomain G’ of Mitochondrial Elongation Factor G1 Is Associated with Combined OXPHOS Deficiency in Fibroblasts but Not in Muscle,” European Journal of Human Genetics, Vol. 19, No. 3, 2011, pp. 275-279. doi:10.1038/ejhg.2010.208
[84] Y. Bykhovskaya, K. Casas, E. Mengesha, A. Inbal and N. Fischel-Ghodsian, “Missense Mutation in Pseudouridine Synthase 1 (PUS1) Causes Mitochondrial Myopathy and Sideroblastic Anemia (MLASA),” The American Journal of Human Genetics, Vol. 74, No. 6, 2004, pp. 1303-1308. doi:10.1086/421530
[85] D. Ghezzi E. Baruffini, T. B. Haack, F Invernizzi, L. Melchionda, C. Dallabona, T. M. Strom, R. Parini, A. B. Burlina, T. Meitinger, H. Prokisch, I. Ferrero and M. Zeviani, “Mutations of the Mitochondrial-tRNA Modifier MTO1 Cause Hypertrophic Cardiomyopathy and Lactic Acidosis,” The American Journal of Human Genetics, Vol. 90, No. 6, 2012, pp. 1079-1087. doi:10.1016/j.ajhg.2012.04.011
[86] E. J. Tucker, S. G. Hershman, C. Kohrer, C. A. Belcher-Timme, J. Patel, et al., “Mutations in MTFMT Underliea Human Disorder of Formylation causIng Impaired Mitochondrial Translation,” Cell Metabolism, Vol. 14, No. 3, 2011, pp. 428-434.

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