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Journal of Biomedicine and Biotechnology
Volume 2010 (2010), Article ID 737385, 24 pages
doi:10.1155/2010/737385
Review Article

Mitochondrial Translation and Beyond: Processes Implicated in Combined Oxidative Phosphorylation Deficiencies

Paulien Smits, Jan Smeitink, and Lambert van den Heuvel

Department of Pediatrics, Nijmegen Center for Mitochondrial Disorders, Radboud University Nijmegen Medical Center, Geert Grooteplein 10, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands

Received 31 October 2009; Accepted 29 January 2010

Academic Editor: Aikaterini Kontrogianni-Konstantopoulos

Copyright © 2010 Paulien Smits et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. W. Gray, G. Burger, and B. F. Lang, “Mitochondrial evolution,” Science, vol. 283, no. 5407, pp. 1476–1481, 1999. View at Publisher · View at Google Scholar
  2. K.-D. Gerbitz, K. Gempel, and D. Brdiczka, “Mitochondria and diabetes: genetic, biochemical, and clinical implications of the cellular energy circuit,” Diabetes, vol. 45, no. 2, pp. 113–126, 1996.
  3. K. Hojlund, M. Mogensen, K. Sahlin, and H. Beck-Nielsen, “Mitochondrial dysfunction in type 2 diabetes and obesity,” Endocrinology and Metabolism Clinics of North America, vol. 37, no. 3, pp. 713–731, 2008. View at Publisher · View at Google Scholar · View at PubMed
  4. W. Mandemakers, V. A. Morais, and B. De Strooper, “A cell biological perspective on mitochondrial dysfunction in Parkinson disease and other neurodegenerative diseases,” Journal of Cell Science, vol. 120, no. 10, pp. 1707–1716, 2007. View at Publisher · View at Google Scholar · View at PubMed
  5. D. C. Chan, “Mitochondria: dynamic organelles in disease, aging, and development,” Cell, vol. 125, no. 7, pp. 1241–1252, 2006. View at Publisher · View at Google Scholar · View at PubMed
  6. L. Guarente, “Mitochondria—a nexus for aging, calorie restriction, and sirtuins?” Cell, vol. 132, no. 2, pp. 171–176, 2008. View at Publisher · View at Google Scholar · View at PubMed
  7. A. M. Schaefer, R. W. Taylor, D. M. Turnbull, and P. F. Chinnery, “The epidemiology of mitochondrial disorders—past, present and future,” Biochimica et Biophysica Acta, vol. 1659, no. 2-3, pp. 115–120, 2004. View at Publisher · View at Google Scholar · View at PubMed
  8. M. Saraste, “Oxidative phosphorylation at the fin de siecle,” Science, vol. 283, no. 5407, pp. 1488–1493, 1999. View at Publisher · View at Google Scholar
  9. J. L. C. M. Loeffen, J. A. M. Smeitink, J. M. F. Trijbels, et al., “Isolated complex I deficiency in children: clinical, biochemical and genetic aspects,” Human Mutation, vol. 15, no. 2, pp. 123–134, 2000. View at Publisher · View at Google Scholar
  10. F.-G. Debray, M. Lambert, and G. A. Mitchell, “Disorders of mitochondrial function,” Current Opinion in Pediatrics, vol. 20, no. 4, pp. 471–482, 2008. View at Publisher · View at Google Scholar · View at PubMed
  11. M. Zeviani and S. Di Donato, “Mitochondrial disorders,” Brain, vol. 127, no. 10, pp. 2153–2172, 2004. View at Publisher · View at Google Scholar · View at PubMed
  12. “MITOMAP: A Human Mitochondrial Genome Database,” 2009, http://www.mitomap.org/MITOMAP.
  13. W. C. Copeland, “Inherited mitochondrial diseases of DNA replication,” Annual Review of Medicine, vol. 59, pp. 131–146, 2008. View at Publisher · View at Google Scholar · View at PubMed
  14. 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),” American Journal of Human Genetics, vol. 74, no. 6, pp. 1303–1308, 2004. View at Publisher · View at Google Scholar · View at PubMed
  15. M. J. H. Coenen, H. Antonicka, C. Ugalde, et al., “Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency,” New England Journal of Medicine, vol. 351, no. 20, pp. 2080–2086, 2004. View at Publisher · View at Google Scholar · View at PubMed
  16. S. Edvardson, A. Shaag, O. Kolesnikova, et al., “Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia,” American Journal of Human Genetics, vol. 81, no. 4, pp. 857–862, 2007. View at Publisher · View at Google Scholar · View at PubMed
  17. E. Fernandez-Vizarra, A. Berardinelli, L. Valente, V. Tiranti, and M. Zeviani, “Nonsense mutation in pseudouridylate synthase 1 (PUS1) in two brothers affected by myopathy, lactic acidosis and sideroblastic anaemia (MLASA),” Journal of Medical Genetics, vol. 44, no. 3, pp. 173–180, 2007. View at Publisher · View at Google Scholar · View at PubMed
  18. C. Miller, A. Saada, N. Shaul, et al., “Defective mitochondrial translation caused by a ribosomal protein (MRPS16) mutation,” Annals of Neurology, vol. 56, no. 5, pp. 734–738, 2004. View at Publisher · View at Google Scholar · View at PubMed
  19. A. Saada, A. Shaag, S. Arnon, et al., “Antenatal mitochondrial disease caused by mitochondrial ribosomal protein (MRPS22) mutation,” Journal of Medical Genetics, vol. 44, no. 12, pp. 784–786, 2007. View at Publisher · View at Google Scholar · View at PubMed
  20. G. C. Scheper, T. van der Klok, R. J. van Andel, et al., “Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation,” Nature Genetics, vol. 39, no. 4, pp. 534–539, 2007. View at Publisher · View at Google Scholar · View at PubMed
  21. J. A. M. Smeitink, O. Elpeleg, H. Antonicka, et al., “Distinct clinical phenotypes associated with a mutation in the mitochondrial translation elongation factor EFTs,” American Journal of Human Genetics, vol. 79, no. 5, pp. 869–877, 2006. View at Publisher · View at Google Scholar · View at PubMed
  22. L. Valente, V. Tiranti, R. M. Marsano, et al., “Infantile encephalopathy and defective mitochondrial DNA translation in patients with mutations of mitochondrial elongation factors EFG1 and EFTu,” American Journal of Human Genetics, vol. 80, no. 1, pp. 44–58, 2007. View at Publisher · View at Google Scholar · View at PubMed
  23. P. Isohanni, T. Linnankivi, J. Buzkova, et al., “DARS2 mutations in mitochondrial leucoencephalopathy and multiple sclerosis,” Journal of Medical Genetics, vol. 47, no. 1, pp. 66–70, 2010. View at Publisher · View at Google Scholar · View at PubMed
  24. A. Zeharia, A. Shaag, O. Pappo, et al., “Acute infantile liver failure due to mutations in the TRMU gene,” American Journal of Human Genetics, vol. 85, no. 3, pp. 401–407, 2009. View at Publisher · View at Google Scholar · View at PubMed
  25. 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, pp. 1835–1846, 2006. View at Publisher · View at Google Scholar · View at PubMed
  26. S. Anderson, A. T. Bankier, and B. G. Barrell, “Sequence and organization of the human mitochondrial genome,” Nature, vol. 290, no. 5806, pp. 457–465, 1981.
  27. W. M. Brown, M. George Jr., and A. C. Wilson, “Rapid evolution of animal mitochondrial DNA,” Proceedings of the National Academy of Sciences of the United States of America, vol. 76, no. 4, pp. 1967–1971, 1979.
  28. M. Lynch, B. Koskella, and S. Schaack, “Mutation pressure and the evolution of organelle genomic architecture,” Science, vol. 311, no. 5768, pp. 1727–1730, 2006. View at Publisher · View at Google Scholar · View at PubMed
  29. C. Richter, J.-W. Park, and B. N. Ames, “Normal oxidative damage to mitochondrial and nuclear DNA is extensive,” Proceedings of the National Academy of Sciences of the United States of America, vol. 85, no. 17, pp. 6465–6467, 1988.
  30. R. W. Taylor and D. M. Turnbull, “Mitochondrial DNA mutations in human disease,” Nature Reviews Genetics, vol. 6, no. 5, pp. 389–402, 2005. View at Publisher · View at Google Scholar · View at PubMed
  31. D. Bogenhagen and D. A. Clayton, “Mouse l cell mitochondrial DNA molecules are selected randomly for replication throughout the cell cycle,” Cell, vol. 11, no. 4, pp. 719–727, 1977.
  32. D. A. Clayton, “Replication of animal mitochondrial DNA,” Cell, vol. 28, no. 4, pp. 693–705, 1982.
  33. G. S. Shadel and D. A. Clayton, “Mitochondrial DNA maintenance in vertebrates,” Annual Review of Biochemistry, vol. 66, pp. 409–436, 1997. View at Publisher · View at Google Scholar · View at PubMed
  34. I. J. Holt, H. E. Lorimer, and H. T. Jacobs, “Coupled leading- and lagging-strand synthesis of mammalian mitochondrial DNA,” Cell, vol. 100, no. 5, pp. 515–524, 2000.
  35. T. Yasukawa, M.-Y. Yang, H. T. Jacobs, and I. J. Holt, “A bidirectional origin of replication maps to the major noncoding region of human mitochondrial DNA,” Molecular Cell, vol. 18, no. 6, pp. 651–662, 2005. View at Publisher · View at Google Scholar · View at PubMed
  36. M. A. Graziewicz, M. J. Longley, and W. C. Copeland, “DNA polymerase γ in mitochondrial DNA replication and repair,” Chemical Reviews, vol. 106, no. 2, pp. 383–405, 2006. View at Publisher · View at Google Scholar · View at PubMed
  37. I. J. Holt, J. He, C.-C. Mao, et al., “Mammalian mitochondrial nucleoids: organizing an independently minded genome,” Mitochondrion, vol. 7, no. 5, pp. 311–321, 2007. View at Publisher · View at Google Scholar · View at PubMed
  38. F. Malka, A. Lombès, and M. Rojo, “Organization, dynamics and transmission of mitochondrial DNA: focus on vertebrate nucleoids,” Biochimica et Biophysica Acta, vol. 1763, no. 5-6, pp. 463–472, 2006. View at Publisher · View at Google Scholar · View at PubMed
  39. N. B. Larsen, M. Rasmussen, and L. J. Rasmussen, “Nuclear and mitochondrial DNA repair: similar pathways?” Mitochondrion, vol. 5, no. 2, pp. 89–108, 2005. View at Publisher · View at Google Scholar · View at PubMed
  40. J. A. Stuart and M. F. Brown, “Mitochondrial DNA maintenance and bioenergetics,” Biochimica et Biophysica Acta, vol. 1757, no. 2, pp. 79–89, 2006. View at Publisher · View at Google Scholar · View at PubMed
  41. A. Saada, “Deoxyribonucleotides and disorders of mitochondrial DNA integrity,” DNA and Cell Biology, vol. 23, no. 12, pp. 797–806, 2004. View at Publisher · View at Google Scholar · View at PubMed
  42. A. Spinazzola and M. Zeviani, “Disorders of nuclear-mitochondrial intergenomic signaling,” Gene, vol. 354, no. 1-2, pp. 162–168, 2005. View at Publisher · View at Google Scholar · View at PubMed
  43. D. M. Kirby and D. R. Thorburn, “Approaches to finding the molecular basis of mitochondrial oxidative phosphorylation disorders,” Twin Research and Human Genetics, vol. 11, no. 4, pp. 395–411, 2008. View at Publisher · View at Google Scholar · View at PubMed
  44. N. D. Bonawitz, D. A. Clayton, and G. S. Shadel, “Initiation and beyond: multiple functions of the human mitochondrial transcription machinery,” Molecular Cell, vol. 24, no. 6, pp. 813–825, 2006. View at Publisher · View at Google Scholar · View at PubMed
  45. M. Falkenberg, N.-G. Larsson, and C. M. Gustafsson, “DNA replication and transcription in mammalian mitochondria,” Annual Review of Biochemistry, vol. 76, pp. 679–699, 2007. View at Publisher · View at Google Scholar · View at PubMed
  46. M. Roberti, P. L. Polosa, F. Bruni, et al., “The MTERF family proteins: mitochondrial transcription regulators and beyond,” Biochimica et Biophysica Acta, vol. 1787, no. 5, pp. 303–311, 2009. View at Publisher · View at Google Scholar · View at PubMed
  47. A. K. Hyvärinen, J. L. O. Pohjoismäki, A. Reyes, et al., “The mitochondrial transcription termination factor mTERF modulates replication pausing in human mitochondrial DNA,” Nucleic Acids Research, vol. 35, no. 19, pp. 6458–6474, 2007. View at Publisher · View at Google Scholar · View at PubMed
  48. T. Linder, C. B. Park, J. Asin-Cayuela, et al., “A family of putative transcription termination factors shared amongst metazoans and plants,” Current Genetics, vol. 48, no. 4, pp. 265–269, 2005. View at Publisher · View at Google Scholar · View at PubMed
  49. Y. Chen, G. Zhou, M. Yu, et al., “Cloning and functional analysis of human mTERFL encoding a novel mitochondrial transcription termination factor-like protein,” Biochemical and Biophysical Research Communications, vol. 337, no. 4, pp. 1112–1118, 2005. View at Publisher · View at Google Scholar · View at PubMed
  50. M. Pellegrini, J. Asin-Cayuela, H. Erdjument-Bromage, P. Tempst, N.-G. Larsson, and C. M. Gustafsson, “MTERF2 is a nucleoid component in mammalian mitochondria,” Biochimica et Biophysica Acta, vol. 1787, no. 5, pp. 296–302, 2009. View at Publisher · View at Google Scholar · View at PubMed
  51. T. Wenz, C. Luca, A. Torraco, and C. T. Moraes, “mTERF2 regulates oxidative phosphorylation by modulating mtDNA transcription,” Cell Metabolism, vol. 9, no. 6, pp. 499–511, 2009. View at Publisher · View at Google Scholar · View at PubMed
  52. C. B. Park, J. Asin-Cayuela, Y. Cámara, et al., “MTERF3 is a negative regulator of mammalian mtDNA transcription,” Cell, vol. 130, no. 2, pp. 273–285, 2007. View at Publisher · View at Google Scholar · View at PubMed
  53. M. Roberti, F. Bruni, P. Loguercio Polosa, C. Manzari, M. N. Gadaleta, and P. Cantatore, “MTERF3, the most conserved member of the mTERF-family, is a modular factor involved in mitochondrial protein synthesis,” Biochimica et Biophysica Acta, vol. 1757, no. 9-10, pp. 1199–1206, 2006. View at Publisher · View at Google Scholar · View at PubMed
  54. A. Cayuela, Y. Shi, and C. M. Gustafsson, “Initial characterization of MTERF4, a paralogue of MTERF1 (mTERF),” in Proceedings of the 7th European Meeting on Mitochondrial Pathology (EUROMIT '08), p. 20, Stockholm, Sweden, June 2008, abstract no. 14.
  55. D. Ojala, J. Montoya, and G. Attardi, “tRNA punctuation model of RNA processing in human mitochondria,” Nature, vol. 290, no. 5806, pp. 470–474, 1981.
  56. J. Montoya, M. J. López-Pérez, and E. Ruiz-Pesini, “Mitochondrial DNA transcription and diseases: past, present and future,” Biochimica et Biophysica Acta, vol. 1757, no. 9-10, pp. 1179–1189, 2006. View at Publisher · View at Google Scholar · View at PubMed
  57. D. Gagliardi, P. P. Stepien, R. J. Temperley, R. N. Lightowlers, and Z. M. A. Chrzanowska-Lightowlers, “Messenger RNA stability in mitochondria: different means to an end,” Trends in Genetics, vol. 20, no. 6, pp. 260–267, 2004. View at Publisher · View at Google Scholar · View at PubMed
  58. H.-W. Chen, C. M. Koehler, and M. A. Teitell, “Human polynucleotide phosphorylase: location matters,” Trends in Cell Biology, vol. 17, no. 12, pp. 600–608, 2007. View at Publisher · View at Google Scholar · View at PubMed
  59. L. Khidr, G. Wu, A. Davila, V. Procaccio, D. Wallace, and W.-H. Lee, “Role of SUV3 helicase in maintaining mitochondrial homeostasis in human cells,” Journal of Biological Chemistry, vol. 283, no. 40, pp. 27064–27073, 2008. View at Publisher · View at Google Scholar · View at PubMed
  60. A. Chomyn, A. Martinuzzi, M. Yoneda, et al., “MELAS mutation in mtDNA binding site for transcription termination factor causes defects in protein synthesis and in respiration but no change in levels of upstream and downstream mature transcripts,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 10, pp. 4221–4225, 1992. View at Publisher · View at Google Scholar
  61. J. F. Hess, M. A. Parisi, J. L. Bennett, and D. A. Clayton, “Impairment of mitochondrial transcription termination by a point mutation associated with the MELAS subgroup of mitochondrial encephalomyopathies,” Nature, vol. 351, no. 6323, pp. 236–239, 1991. View at Publisher · View at Google Scholar · View at PubMed
  62. M.-X. Guan, Q. Yan, X. Li, et al., “Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12S ribosomal RNA mutations,” American Journal of Human Genetics, vol. 79, no. 2, pp. 291–302, 2006. View at Publisher · View at Google Scholar · View at PubMed
  63. C. Knox, E. Sass, W. Neupert, and O. Pines, “Import into mitochondria, folding and retrograde movement of fumarase in yeast,” Journal of Biological Chemistry, vol. 273, no. 40, pp. 25587–25593, 1998. View at Publisher · View at Google Scholar
  64. J. A. MacKenzie and R. M. Payne, “Ribosomes specifically bind to mammalian mitochondria via protease-sensitive proteins on the outer membrane,” Journal of Biological Chemistry, vol. 279, no. 11, pp. 9803–9810, 2004. View at Publisher · View at Google Scholar · View at PubMed
  65. K. Verner, “Co-translational protein import into mitochondria: an alternative view,” Trends in Biochemical Sciences, vol. 18, no. 10, pp. 366–371, 1993. View at Publisher · View at Google Scholar
  66. P. Marc, A. Margeot, F. Devaux, C. Blugeon, M. Corral-Debrinski, and C. Jacq, “Genome-wide analysis of mRNAs targeted to yeast mitochondria,” EMBO Reports, vol. 3, no. 2, pp. 159–164, 2002. View at Publisher · View at Google Scholar · View at PubMed
  67. A. Mukhopadhyay, L. Ni, and H. Weiner, “A co-translational model to explain the in vivo import of proteins into HeLa cell mitochondria,” Biochemical Journal, vol. 382, no. 1, pp. 385–392, 2004. View at Publisher · View at Google Scholar · View at PubMed
  68. M. Garcia, X. Darzacq, T. Delaveau, L. Jourdren, R. H. Singer, and C. Jacq, “Mitochondria-associated yeast mRNAs and the biogenesis of molecular complexes,” Molecular Biology of the Cell, vol. 18, no. 2, pp. 362–368, 2007. View at Publisher · View at Google Scholar · View at PubMed
  69. A. Margeot, M. Garcia, W. Wang, E. Tetaud, J. P. di Rago, and C. Jacq, “Why are many mRNAs translated to the vicinity of mitochondria: a role in protein complex assembly?” Gene, vol. 354, no. 1-2, pp. 64–71, 2005. View at Publisher · View at Google Scholar · View at PubMed
  70. F. J. Iborra, H. Kimura, and P. R. Cook, “The functional organization of mitochondrial genomes in human cells,” BMC Biology, vol. 2, article 9, 2004. View at Publisher · View at Google Scholar · View at PubMed
  71. W. Neupert and J. M. Herrmann, “Translocation of proteins into mitochondria,” Annual Review of Biochemistry, vol. 76, pp. 723–749, 2007. View at Publisher · View at Google Scholar · View at PubMed
  72. N. Wiedemann, A. E. Frazier, and N. Pfanner, “The protein import machinery of mitochondria,” Journal of Biological Chemistry, vol. 279, no. 15, pp. 14473–14476, 2004. View at Publisher · View at Google Scholar · View at PubMed
  73. J. R. Blesa, A. Solano, P. Briones, J. A. Prieto-Ruiz, J. Hernández-Yago, and F. Coria, “Molecular genetics of a patient with Mohr-Tranebjaerg syndrome due to a new mutation in the DDP1 gene,” NeuroMolecular Medicine, vol. 9, no. 4, pp. 285–291, 2007. View at Publisher · View at Google Scholar · View at PubMed
  74. K. Roesch, S. P. Curran, L. Tranebjaerg, and C. M. Koehler, “Human deafness dystonia syndrome is caused by a defect in assembly of the DDP1/TIMM8a-TIMM13 complex,” Human Molecular Genetics, vol. 11, no. 5, pp. 477–486, 2002.
  75. J. Binder, S. Hofmann, S. Kreisel, et al., “Clinical and molecular findings in a patient with a novel mutation in the deafness-dystonia peptide (DDP1) gene,” Brain, vol. 126, no. 8, pp. 1814–1820, 2003. View at Publisher · View at Google Scholar · View at PubMed
  76. K. M. Davey, J. S. Parboosingh, D. R. McLeod, et al., “Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition,” Journal of Medical Genetics, vol. 43, no. 5, pp. 385–393, 2006. View at Publisher · View at Google Scholar · View at PubMed
  77. D. Mokranjac, M. Sichting, W. Neupert, and K. Hell, “Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria,” EMBO Journal, vol. 22, no. 19, pp. 4945–4956, 2003. View at Publisher · View at Google Scholar · View at PubMed
  78. X. Pérez-Martínez, S. Funes, Y. Camacho-Villasana, S. Marjavaara, F. Tavares-Carreón, and M. Shingú-Vázquez, “Protein synthesis and assembly in mitochondrial disorders,” Current Topics in Medicinal Chemistry, vol. 8, no. 15, pp. 1335–1350, 2008. View at Publisher · View at Google Scholar
  79. S. Osawa, T. H. Jukes, K. Watanabe, and A. Muto, “Recent evidence for evolution of the genetic code,” Microbiological Reviews, vol. 56, no. 1, pp. 229–264, 1992.
  80. J. Montoya, D. Ojala, and G. Attardi, “Distinctive features of the 5′-terminal sequences of the human mitochondrial mRNAs,” Nature, vol. 290, no. 5806, pp. 465–470, 1981.
  81. K. Grohmann, F. Amalric, S. Crews, and G. Attardi, “Failure to detect “cap” structures in mitochondrial DNA-coded poly(A)-containing RNA from HeLa cells,” Nucleic Acids Research, vol. 5, no. 3, pp. 637–651, 1978.
  82. H.-X. Liao and L. L. Spremulli, “Interaction of bovine mitochondrial ribosomes with messenger RNA,” Journal of Biological Chemistry, vol. 264, no. 13, pp. 7518–7522, 1989.
  83. B. S. Laursen, H. P. Sørensen, K. K. Mortensen, and H. U. Sperling-Petersen, “Initiation of protein synthesis in bacteria,” Microbiology and Molecular Biology Reviews, vol. 69, no. 1, pp. 101–123, 2005. View at Publisher · View at Google Scholar · View at PubMed
  84. M. López-Lastra, A. Rivas, and M. I. Barría, “Protein synthesis in eukaryotes: the growing biological relevance of cap-independent translation initiation,” Biological Research, vol. 38, no. 2-3, pp. 121–146, 2005.
  85. B. G. Barrell, S. Anderson, and A. T. Bankier, “Different pattern of codon recognition by mammalian mitochondrial tRNAs,” Proceedings of the National Academy of Sciences of the United States of America, vol. 77, no. 6, pp. 3164–3166, 1980.
  86. R. Mikelsaar, “Human mitochondrial genome and the evolution of methionine transfer ribonucleic acids,” Journal of Theoretical Biology, vol. 105, no. 2, pp. 221–232, 1983.
  87. A. Marintchev and G. Wagner, “Translation initiation: structures, mechanisms and evolution,” Quarterly Reviews of Biophysics, vol. 37, no. 3-4, pp. 197–284, 2004. View at Publisher · View at Google Scholar · View at PubMed
  88. A. Roll-Mecak, B.-S. Shin, T. E. Dever, and S. K. Burley, “Engaging the ribosome: universal IFs of translation,” Trends in Biochemical Sciences, vol. 26, no. 12, pp. 705–709, 2001. View at Publisher · View at Google Scholar
  89. 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, pp. 1859–1865, 1995. View at Publisher · View at Google Scholar
  90. E. C. Koc and L. L. Spremulli, “Identification of mammalian mitochondrial translational initiation factor 3 and examination of its role in initiation complex formation with natural mRNAs,” Journal of Biological Chemistry, vol. 277, no. 38, pp. 35541–35549, 2002. View at Publisher · View at Google Scholar · View at PubMed
  91. L. L. Spremulli, A. Coursey, T. Navratil, and S. E. Hunter, “Initiation and elongation factors in mammalian mitochondrial protein biosynthesis,” Progress in Nucleic Acid Research and Molecular Biology, vol. 77, pp. 211–261, 2004. View at Publisher · View at Google Scholar · View at PubMed
  92. R. Gaur, D. Grasso, P. P. Datta, et al., “A single mammalian mitochondrial translation initiation factor functionally replaces two bacterial factors,” Molecular Cell, vol. 29, no. 2, pp. 180–190, 2008. View at Publisher · View at Google Scholar · View at PubMed
  93. M. Hammarsund, W. Wilson, M. Corcoran, et al., “Identification and characterization of two novel human mitochondrial elongation factor genes, hEFG2 and hEFG1, phylogenetically conserved through evolution,” Human Genetics, vol. 109, no. 5, pp. 542–550, 2001. View at Publisher · View at Google Scholar · View at PubMed
  94. M. Ling, F. Merante, H.-S. Chen, C. Duff, A. M. V. Duncan, and B. H. Robinson, “The human mitochondrial elongation factor tu (EF-Tu) gene: CDNA sequence, genomic localization, genomic structure, and identification of a pseudogene,” Gene, vol. 197, no. 1-2, pp. 325–336, 1997. View at Publisher · View at Google Scholar
  95. H. Xin, V. Woriax, W. Burkhart, and L. L. Spremulli, “Cloning and expression of mitochondrial translational elongation factor Ts from bovine and human liver,” Journal of Biological Chemistry, vol. 270, no. 29, pp. 17243–17249, 1995. View at Publisher · View at Google Scholar
  96. K. Bhargava, P. Templeton, and L. L. Spremulli, “Expression and characterization of isoform 1 of human mitochondrial elongation factor G,” Protein Expression and Purification, vol. 37, no. 2, pp. 368–376, 2004. View at Publisher · View at Google Scholar · View at PubMed
  97. E. A. Winzeler, D. D. Shoemaker, A. Astromoff, et al., “Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis,” Science, vol. 285, no. 5429, pp. 901–906, 1999. View at Publisher · View at Google Scholar
  98. M. Tsuboi, H. Morita, Y. Nozaki, et al., “EF-G2mt is an exclusive recycling factor in mammalian mitochondrial protein synthesis,” Molecular Cell, vol. 35, no. 4, pp. 502–510, 2009. View at Publisher · View at Google Scholar · View at PubMed
  99. G. Bertram, S. Innes, O. Minella, J. P. Richardson, and I. Stansfield, “Endless possibilities: translation termination and stop codon recognition,” Microbiology, vol. 147, no. 2, pp. 255–269, 2001.
  100. L. D. Kapp and J. R. Lorsch, “The molecular mechanics of eukaryotic translation,” Annual Review of Biochemistry, vol. 73, pp. 657–704, 2004. View at Publisher · View at Google Scholar · View at PubMed
  101. Y. Nozaki, N. Matsunaga, T. Ishizawa, T. Ueda, and N. Takeuchi, “HMRF1L is a human mitochondrial translation release factor involved in the decoding of the termination codons UAA and UAG,” Genes to Cells, vol. 13, no. 5, pp. 429–438, 2008. View at Publisher · View at Google Scholar · View at PubMed
  102. H. R. Soleimanpour-Lichaei, I. Kühl, M. Gaisne, et al., “mtRF1a is a human mitochondrial translation release factor decoding the major termination codons UAA and UAG,” Molecular Cell, vol. 27, no. 5, pp. 745–757, 2007. View at Publisher · View at Google Scholar · View at PubMed
  103. Y. Zhang and L. L. Spremulli, “Identification and cloning of human mitochondrial translational release factor 1 and the ribosome recycling factor,” Biochimica et Biophysica Acta, vol. 1443, no. 1-2, pp. 245–250, 1998. View at Publisher · View at Google Scholar
  104. J. Rorbach, R. Richter, H. J. Wessels, et al., “The human mitochondrial ribosome recycling factor is essential for cell viability,” Nucleic Acids Research, vol. 36, no. 18, pp. 5787–5799, 2008. View at Publisher · View at Google Scholar · View at PubMed
  105. M. J. Bibb, R. A. Van Etten, C. T. Wright, M. W. Walberg, and D. A. Clayton, “Sequence and gene organization of mouse mitochondrial DNA,” Cell, vol. 26, no. 2, pp. 167–180, 1981.
  106. G. Gadaleta, G. Pepe, G. De Candia, C. Quagliariello, E. Sbisa, and C. Saccone, “The complete nucleotide sequence of the Rattus norvegicus mitochondrial genome: cryptic signals revealed by comparative analysis between vertebrates,” Journal of Molecular Evolution, vol. 28, no. 6, pp. 497–516, 1989.
  107. P. Smits, J. A. M. Smeitink, L. P. van den Heuvel, M. A. Huynen, and T. J. G. Ettema, “Reconstructing the evolution of the mitochondrial ribosomal proteome,” Nucleic Acids Research, vol. 35, no. 14, pp. 4686–4703, 2007. View at Publisher · View at Google Scholar · View at PubMed
  108. T. W. O'Brien, “Properties of human mitochondrial ribosomes,” IUBMB Life, vol. 55, no. 9, pp. 505–513, 2003. View at Publisher · View at Google Scholar · View at PubMed
  109. M. R. Sharma, E. C. Koc, P. P. Datta, T. M. Booth, L. L. Spremulli, and R. K. Agrawal, “Structure of the mammalian mitochondrial ribosome reveals an expanded functional role for its component proteins,” Cell, vol. 115, no. 1, pp. 97–108, 2003. View at Publisher · View at Google Scholar
  110. M. Helm, H. Brulé, D. Friede, R. Giegé, D. Pütz, and C. Florentz, “Search for characteristic structural features of mammalian mitochondrial tRNAs,” RNA, vol. 6, no. 10, pp. 1356–1379, 2000. View at Publisher · View at Google Scholar
  111. M. Helm, “Post-transcriptional nucleotide modification and alternative folding of RNA,” Nucleic Acids Research, vol. 34, no. 2, pp. 721–733, 2006. View at Publisher · View at Google Scholar · View at PubMed
  112. M. Helm, R. Giegé, and C. Florentz, “A Watson-Crick base-pair-disrupting methyl group (m1A9) is sufficient for cloverleaf folding of human mitochondrial tRNA(Lys),” Biochemistry, vol. 38, no. 40, pp. 13338–13346, 1999. View at Publisher · View at Google Scholar
  113. Y. Kirino and T. Suzuki, “Human mitochondrial diseases associated with tRNA wobble modification deficiency,” RNA Biology, vol. 2, no. 2, pp. 41–44, 2005.
  114. R. Giegé, M. Sissler, and C. Florentz, “Universal rules and idiosyncratic features in tRNA identity,” Nucleic Acids Research, vol. 26, no. 22, pp. 5017–5035, 1998.
  115. L. Bonnefond, A. Fender, J. Rudinger-Thirion, R. Giegé, C. Florentz, and M. Sissler, “Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS,” Biochemistry, vol. 44, no. 12, pp. 4805–4816, 2005. View at Publisher · View at Google Scholar · View at PubMed
  116. S. M. K. Davies, O. Rackham, A.-M. J. Shearwood, et al., “Pentatricopeptide repeat domain protein 3 associates with the mitochondrial small ribosomal subunit and regulates translation,” FEBS Letters, vol. 583, no. 12, pp. 1853–1858, 2009. View at Publisher · View at Google Scholar · View at PubMed
  117. V. Ramakrishnan, “Ribosome structure and the mechanism of translation,” Cell, vol. 108, no. 4, pp. 557–572, 2002. View at Publisher · View at Google Scholar
  118. C. N. Jones, K. A. Wilkinson, K. T. Hung, K. M. Weeks, and L. L. Spremulli, “Lack of secondary structure characterizes the 5′ ends of mammalian mitochondrial mRNAs,” RNA, vol. 14, no. 5, pp. 862–871, 2008. View at Publisher · View at Google Scholar · View at PubMed
  119. B. E. Christian and L. L. Spremulli, “Evidence for an active role of IF3mt in the initiation of translation in mammalian mitochondria,” Biochemistry, vol. 48, no. 15, pp. 3269–3278, 2009. View at Publisher · View at Google Scholar · View at PubMed
  120. K. Bhargava and L. L. Spremulli, “Role of the N- and C-terminal extensions on the activity of mammalian mitochondrial translational initiation factor 3,” Nucleic Acids Research, vol. 33, no. 22, pp. 7011–7018, 2005. View at Publisher · View at Google Scholar · View at PubMed
  121. 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, pp. 13618–13622, 1990.
  122. J. Ma and L. L. Spremulli, “Expression, purification, and mechanistic studies of bovine mitochondrial translational initiation factor 2,” Journal of Biological Chemistry, vol. 271, no. 10, pp. 5805–5811, 1996. View at Publisher · View at Google Scholar
  123. Md. E. Haque, D. Grasso, and L. L. Spremulli, “The interaction of mammalian mitochondrial translational initiation factor 3 with ribosomes: evolution of terminal extensions in IF3mt,” Nucleic Acids Research, vol. 36, no. 2, pp. 589–597, 2008. View at Publisher · View at Google Scholar · View at PubMed
  124. Y.-C. Cai, J. M. Bullard, N. L. Thompson, and L. L. Spremulli, “Interaction of mitochondrial elongation factor Tu with aminoacyl-tRNA and elongation factor Ts,” Journal of Biological Chemistry, vol. 275, no. 27, pp. 20308–20314, 2000. View at Publisher · View at Google Scholar · View at PubMed
  125. V. L. Woriax, J. M. Bullard, L. Ma, T. Yokogawa, and L. L. Spremulli, “Mechanistic studies of the translational elongation cycle in mammalian mitochondria,” Biochimica et Biophysica Acta, vol. 1352, no. 1, pp. 91–101, 1997. View at Publisher · View at Google Scholar
  126. F. Sasarman, H. Antonicka, and E. A. Shoubridge, “The A3243G tRNALeu(UUR) MELAS mutation causes amino acid misincorporation and a combined respiratory chain assembly defect partially suppressed by overexpression of EFTu and EFG2,” Human Molecular Genetics, vol. 17, no. 23, pp. 3697–3707, 2008. View at Publisher · View at Google Scholar · View at PubMed
  127. A. Nagao, T. Suzuki, and T. Suzuki, “Aminoacyl-tRNA surveillance by EF-Tu in mammalian mitochondria,” Nucleic Acids Symposium Series, no. 51, pp. 41–42, 2007.
  128. J. A. Mears, J. J. Cannone, S. M. Stagg, R. R. Gutell, R. K. Agrawal, and S. C. Harvey, “Modeling a minimal ribosome based on comparative sequence analysis,” Journal of Molecular Biology, vol. 321, no. 2, pp. 215–234, 2002. View at Publisher · View at Google Scholar
  129. J. A. Mears, M. R. Sharma, R. R. Gutell, et al., “A structural model for the large subunit of the mammalian mitochondrial ribosome,” Journal of Molecular Biology, vol. 358, no. 1, pp. 193–212, 2006. View at Publisher · View at Google Scholar · View at PubMed
  130. J. Towpik, “Regulation of mitochondrial translation in yeast,” Cellular and Molecular Biology Letters, vol. 10, no. 4, pp. 571–594, 2005.
  131. A. Chacinska and M. Boguta, “Coupling of mitochondrial translation with the formation of respiratory complexes in yeast mitochondria,” Acta Biochimica Polonica, vol. 47, no. 4, pp. 973–991, 2000.
  132. X. Zeng, A. Hourset, and A. Tzagoloff, “The Saccharomyces cerevisiae ATP22 gene codes for the mitochondrial ATPase subunit 6-specific translation factor,” Genetics, vol. 175, no. 1, pp. 55–63, 2007. View at Publisher · View at Google Scholar · View at PubMed
  133. E. C. Koc and L. L. Spremulli, “RNA-binding proteins of mammalian mitochondria,” Mitochondrion, vol. 2, no. 4, pp. 277–291, 2003. View at Publisher · View at Google Scholar · View at PubMed
  134. W. Weraarpachai, H. Antonicka, F. Sasarman, 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, pp. 833–837, 2009. View at Publisher · View at Google Scholar · View at PubMed
  135. M. S. Rodeheffer, B. E. Boone, A. C. Bryan, and G. S. Shadel, “Nam1p, a protein involved in RNA processing and translation, is coupled to transcription through an interaction with yeast mitochondrial RNA polymerase,” Journal of Biological Chemistry, vol. 276, no. 11, pp. 8616–8622, 2001. View at Publisher · View at Google Scholar · View at PubMed
  136. V. K. Mootha, P. Lepage, K. Miller, et al., “Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 2, pp. 605–610, 2003. View at Publisher · View at Google Scholar · View at PubMed
  137. G. M. Manthey and J. E. McEwen, “The product of the nuclear gene PET309 is required for translation of mature mRNA and stability or production of intron-containing RNAs derived from the mitochondrial COX1 locus of Saccharomyces cerevisiae,” EMBO Journal, vol. 14, no. 16, pp. 4031–4043, 1995.
  138. F. Xu, C. Morin, G. Mitchell, C. Ackerley, and B. H. Robinson, “The role of the LRPPRC (leucine-rich pentatricopeptide repeal cassette) gene in cytochrome oxidase assembly: mutation causes lowered levels of COX (cytochrome c oxidase) I and COX III mRNA,” Biochemical Journal, vol. 382, no. 1, pp. 331–336, 2004. View at Publisher · View at Google Scholar · View at PubMed
  139. S. Naithani, S. A. Saracco, C. A. Butler, and T. D. Fox, “Interactions among COX1, COX2, and COX3 mRNA-specific translational activator proteins on the inner surface of the mitochondrial inner membrane of Saccharomyces cerevisiae,” Molecular Biology of the Cell, vol. 14, no. 1, pp. 324–333, 2003. View at Publisher · View at Google Scholar · View at PubMed
  140. M. G. Wallis, O. Groudinsky, P. P. Slonimski, and G. Dujardin, “The NAM1 protein (NAM1p), which is selectively required for cox1, cytb and atp6 transcript processing/stabilisation, is located in the yeast mitochondrial matrix,” European Journal of Biochemistry, vol. 222, no. 1, pp. 27–32, 1994. View at Publisher · View at Google Scholar
  141. G. S. Shadel, “Coupling the mitochondrial transcription machinery to human disease,” Trends in Genetics, vol. 20, no. 10, pp. 513–519, 2004. View at Publisher · View at Google Scholar · View at PubMed
  142. S. Mili and S. Piñol-Roma, “LRP130, a pentatricopeptide motif protein with a noncanonical RNA-binding domain, is bound in vivo to mitochondrial and nuclear RNAs,” Molecular and Cellular Biology, vol. 23, no. 14, pp. 4972–4982, 2003. View at Publisher · View at Google Scholar
  143. M. Nolden, S. Ehses, M. Koppen, A. Bernacchia, E. I. Rugarli, and T. Langer, “The m-AAA protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria,” Cell, vol. 123, no. 2, pp. 277–289, 2005. View at Publisher · View at Google Scholar · View at PubMed
  144. G. Casari, M. De Fusco, S. Ciarmatori, et al., “Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease,” Cell, vol. 93, no. 6, pp. 973–983, 1998. View at Publisher · View at Google Scholar
  145. G. S. Shadel, “Expression and maintenance of mitochondrial DNA: new insights into human disease pathology,” American Journal of Pathology, vol. 172, no. 6, pp. 1445–1456, 2008. View at Publisher · View at Google Scholar · View at PubMed
  146. J. Cotney, Z. Wang, and G. S. Shadel, “Relative abundance of the human mitochondrial transcription system and distinct roles for h-mtTFB1 and h-mtTFB2 in mitochondrial biogenesis and gene expression,” Nucleic Acids Research, vol. 35, no. 12, pp. 4042–4054, 2007. View at Publisher · View at Google Scholar · View at PubMed
  147. Y. Bykhovskaya, E. Mengesha, D. Wang, et al., “Human mitochondrial transcription factor B1 as a modifier gene for hearing loss associated with the mitochondrial A1555G mutation,” Molecular Genetics and Metabolism, vol. 82, no. 1, pp. 27–32, 2004. View at Publisher · View at Google Scholar · View at PubMed
  148. M. D. Metodiev, N. Lesko, C. B. Park, et al., “Methylation of 12S rRNA is necessary for in vivo stability of the small subunit of the mammalian mitochondrial ribosome,” Cell Metabolism, vol. 9, no. 4, pp. 386–397, 2009. View at Publisher · View at Google Scholar · View at PubMed
  149. R. C. Scarpulla, “Transcriptional paradigms in mammalian mitochondrial biogenesis and function,” Physiological Reviews, vol. 88, no. 2, pp. 611–638, 2008. View at Publisher · View at Google Scholar · View at PubMed
  150. D. De Rasmo, A. Signorile, E. Roca, and S. Papa, “CAMP response element-binding protein (CREB) is imported into mitochondria and promotes protein synthesis,” FEBS Journal, vol. 276, no. 16, pp. 4325–4333, 2009. View at Publisher · View at Google Scholar · View at PubMed
  151. S.-L. Liang, D. Quirk, and A. Zhou, “RNase L: its biological roles and regulation,” IUBMB Life, vol. 58, no. 9, pp. 508–514, 2006. View at Publisher · View at Google Scholar · View at PubMed
  152. F. Le Roy, M. Silhol, T. Salehzada, and C. Bisbal, “Regulation of mitochondrial mRNA stability by RNase L is translation-dependent and controls IFNα-induced apoptosis,” Cell Death and Differentiation, vol. 14, no. 8, pp. 1406–1413, 2007. View at Publisher · View at Google Scholar · View at PubMed
  153. H. Suzuki, T. Ueda, H. Taguchi, and N. Takeuchi, “Chaperone properties of mammalian mitochondrial translation elongation factor Tu,” Journal of Biological Chemistry, vol. 282, no. 6, pp. 4076–4084, 2007. View at Publisher · View at Google Scholar · View at PubMed
  154. A. Malki, T. Caldas, J. Abdallah, et al., “Peptidase activity of the Escherichia coli Hsp31 chaperone,” Journal of Biological Chemistry, vol. 280, no. 15, pp. 14420–14426, 2005. View at Publisher · View at Google Scholar · View at PubMed
  155. Z. Wang, J. Cotney, and G. S. Shadel, “Human mitochondrial ribosomal protein MRPL12 interacts directly with mitochondrial RNA polymerase to modulate mitochondrial gene expression,” Journal of Biological Chemistry, vol. 282, no. 17, pp. 12610–12618, 2007. View at Publisher · View at Google Scholar · View at PubMed
  156. E. C. Koc, A. Ranasinghe, W. Burkhart, et al., “A new face on apoptosis: death-associated protein 3 and PDCD9 are mitochondrial ribosomal proteins,” FEBS Letters, vol. 492, no. 1-2, pp. 166–170, 2001. View at Publisher · View at Google Scholar
  157. W. Voos and K. Röttgers, “Molecular chaperones as essential mediators of mitochondrial biogenesis,” Biochimica et Biophysica Acta, vol. 1592, no. 1, pp. 51–62, 2002. View at Publisher · View at Google Scholar
  158. M. Koppen and T. Langer, “Protein degradation within mitochondria: versatile activities of AAA proteases and other peptidases,” Critical Reviews in Biochemistry and Molecular Biology, vol. 42, no. 3, pp. 221–242, 2007. View at Publisher · View at Google Scholar · View at PubMed
  159. L. G. J. Nijtmans, S. M. Artal, L. A. Grivell, and P. J. Coates, “The mitochondrial PHB complex: roles in mitochondrial respiratory complex assembly, ageing and degenerative disease,” Cellular and Molecular Life Sciences, vol. 59, no. 1, pp. 143–155, 2002. View at Publisher · View at Google Scholar
  160. M. Artal-Sanz and N. Tavernarakis, “Prohibitin and mitochondrial biology,” Trends in Endocrinology and Metabolism, vol. 20, no. 8, pp. 394–401, 2009. View at Publisher · View at Google Scholar · View at PubMed
  161. M. Liu and L. Spremulli, “Interaction of mammalian mitochondrial ribosomes with the inner membrane,” Journal of Biological Chemistry, vol. 275, no. 38, pp. 29400–29406, 2000. View at Publisher · View at Google Scholar · View at PubMed
  162. K. Hell, J. M. Herrmann, E. Pratje, W. Neupert, and R. A. Stuart, “Oxa1p, an essential component of the N-tail protein export machinery in mitochondria,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 5, pp. 2250–2255, 1998. View at Publisher · View at Google Scholar
  163. K. Hell, W. Neupert, and R. A. Stuart, “Oxa1p acts as a general membrane insertion machinery for proteins encoded by mitochondrial DNA,” EMBO Journal, vol. 20, no. 6, pp. 1281–1288, 2001. View at Publisher · View at Google Scholar · View at PubMed
  164. M. Ott, M. Prestele, H. Bauerschmitt, S. Funes, N. Bonnefoy, and J. M. Herrmann, “Mba1, a membrane-associated ribosome receptor in mitochondria,” EMBO Journal, vol. 25, no. 8, pp. 1603–1610, 2006. View at Publisher · View at Google Scholar · View at PubMed
  165. M. E. Sanchirico, T. D. Fox, and T. L. Mason, “Accumulation of mitochondrially synthesized Saccharomyces cerevisiae Cox2p and Cox3p depends on targeting information in untranslated portions of their mRNAs,” EMBO Journal, vol. 17, no. 19, pp. 5796–5804, 1998. View at Publisher · View at Google Scholar · View at PubMed
  166. K. Watson, “The organization of ribosomal granules within mitochondrial structures of aerobic and anaerobic cells of Saccharomyces cerevisae,” Journal of Cell Biology, vol. 55, no. 3, pp. 721–726, 1972.
  167. R. A. Stuart, “Insertion of proteins into the inner membrane of mitochondria: the role of the Oxa1 complex,” Biochimica et Biophysica Acta, vol. 1592, no. 1, pp. 79–87, 2002. View at Publisher · View at Google Scholar
  168. N. Bonnefoy, H. L. Fiumera, G. Dujardin, and T. D. Fox, “Roles of Oxa1-related inner-membrane translocases in assembly of respiratory chain complexes,” Biochimica et Biophysica Acta, vol. 1793, no. 1, pp. 60–70, 2009. View at Publisher · View at Google Scholar · View at PubMed
  169. L. Jia, M. Dienhart, M. Schramp, M. McCauley, K. Hell, and R. A. Stuart, “Yeast Oxa1 interacts with mitochondrial ribosomes: the importance of the C-terminal region of Oxa1,” EMBO Journal, vol. 22, no. 24, pp. 6438–6447, 2003. View at Publisher · View at Google Scholar · View at PubMed
  170. L. Jia, J. Kaur, and R. A. Stuart, “Mapping of the saccharomyces cerevisiae oxa1-mitochondrial ribosome interface and identification of MrpL40, a ribosomal protein in close proximity to oxal and critical for oxidative phosphorylation complex assembly,” Eukaryotic Cell, vol. 8, no. 11, pp. 1792–1802, 2009. View at Publisher · View at Google Scholar · View at PubMed
  171. M. Preuss, K. Leonhard, K. Hell, R. A. Stuart, W. Neupert, and J. M. Herrmann, “Mba1, a novel component of the mitochondrial protein export machinery of the yeast Saccharomyces cerevisiae,” Journal of Cell Biology, vol. 153, no. 5, pp. 1085–1096, 2001. View at Publisher · View at Google Scholar
  172. S. Schlickum, A. Moghekar, J. C. Simpson, et al., “LETM1, a gene deleted in Wolf-Hirschhorn syndrome, encodes an evolutionarily conserved mitochondrial protein,” Genomics, vol. 83, no. 2, pp. 254–261, 2004. View at Publisher · View at Google Scholar
  173. A. E. Frazier, R. D. Taylor, D. U. Mick, et al., “Mdm38 interacts with ribosomes and is a component of the mitochondrial protein export machinery,” Journal of Cell Biology, vol. 172, no. 4, pp. 553–564, 2006. View at Publisher · View at Google Scholar · View at PubMed
  174. L. Piao, Y. Li, S. J. Kim, et al., “Association of LETM1 and mrpl36 contributes to the regulation of mitochondrial ATP production and necrotic cell death,” Cancer Research, vol. 69, no. 8, pp. 3397–3404, 2009. View at Publisher · View at Google Scholar · View at PubMed
  175. S. Tamai, H. Iida, S. Yokota, et al., “Characterization of the mitochondrial protein LETM1, which maintains the mitochondrial tubular shapes and interacts with the AAA-ATPase BCS1L,” Journal of Cell Science, vol. 121, no. 15, pp. 2588–2600, 2008. View at Publisher · View at Google Scholar · View at PubMed
  176. K. S. Dimmer, F. Navoni, A. Casarin, et al., “LETM1, deleted in Wolf-Hirschhorn syndrome is required for normal mitochondrial morphology and cellular viability,” Human Molecular Genetics, vol. 17, no. 2, pp. 201–214, 2008. View at Publisher · View at Google Scholar · View at PubMed
  177. A. S. Lynch and J. C. Wang, “Anchoring of DNA to the bacterial cytoplasmic membrane through cotranscriptional synthesis of polypeptides encoding membrane proteins or proteins for export: a mechanism of plasmid hypernegative supercoiling in mutants deficient in DNA topoisomerase I,” Journal of Bacteriology, vol. 175, no. 6, pp. 1645–1655, 1993.
  178. G. H. Vos-Scheperkeuter and B. Witholt, “Co-translational insertion of envelope proteins: theoretical considerations and implications,” Annales de Microbiologie, vol. 133A, no. 1, pp. 129–138, 1982.
  179. M. Trinei, J.-P. Vannier, M. Beurton-Aimar, and V. Norris, “A hyperstructure approach to mitochondria,” Molecular Microbiology, vol. 53, no. 1, pp. 41–53, 2004. View at Publisher · View at Google Scholar · View at PubMed
  180. E. Fernández-Vizarra, V. Tiranti, and M. Zeviani, “Assembly of the oxidative phosphorylation system in humans: what we have learned by studying its defects,” Biochimica et Biophysica Acta, vol. 1793, no. 1, pp. 200–211, 2009. View at Publisher · View at Google Scholar · View at PubMed
  181. I. Ogilvie, N. G. Kennaway, and E. A. Shoubridge, “A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy,” Journal of Clinical Investigation, vol. 115, no. 10, pp. 2784–2792, 2005. View at Publisher · View at Google Scholar · View at PubMed
  182. R. O. Vogel, R. J. R. J. Janssen, C. Ugalde, et al., “Human mitochondrial complex I assembly is mediated by NDUFAF1,” FEBS Journal, vol. 272, no. 20, pp. 5317–5326, 2005. View at Publisher · View at Google Scholar · View at PubMed
  183. S. J. G. Hoefs, C. E. J. Dieteren, R. J. Rodenburg, et al., “Baculovirus complementation restores a novel NDUFAF2 mutation causing complex I deficiency,” Human Mutation, vol. 30, no. 7, pp. E728–E736, 2009. View at Publisher · View at Google Scholar · View at PubMed
  184. A. Saada, R. O. Vogel, S. J. Hoefs, et al., “Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting complex I assembly protein, cause fatal neonatal mitochondrial disease,” American Journal of Human Genetics, vol. 84, no. 6, pp. 718–727, 2009. View at Publisher · View at Google Scholar · View at PubMed
  185. A. Saada, S. Edvardson, M. Rapoport, et al., “C6ORF66 is an assembly factor of mitochondrial complex I,” American Journal of Human Genetics, vol. 82, no. 1, pp. 32–38, 2008. View at Publisher · View at Google Scholar · View at PubMed
  186. R. O. Vogel, R. J. R. J. Janssen, M. A. M. van den Brand, et al., “Cytosolic signaling protein Ecsit also localizes to mitochondria where it interacts with chaperone NDUFAF1 and functions in complex I assembly,” Genes and Development, vol. 21, no. 5, pp. 615–624, 2007. View at Publisher · View at Google Scholar · View at PubMed
  187. D. J. Pagliarini, S. E. Calvo, B. Chang, et al., “A mitochondrial protein compendium elucidates complex I disease biology,” Cell, vol. 134, no. 1, pp. 112–123, 2008. View at Publisher · View at Google Scholar · View at PubMed
  188. M. Gerards, W. Sluiter, B. J. van den Bosch, et al., “Defective complex I assembly due to C20orf7 mutations as a new cause of Leigh syndrome,” Journal of Medical Genetics. In press.
  189. C. Sugiana, D. J. Pagliarini, M. McKenzie, et al., “Mutation of C20orf7 disrupts complex I assembly and causes lethal neonatal mitochondrial disease,” American Journal of Human Genetics, vol. 83, no. 4, pp. 468–478, 2008. View at Publisher · View at Google Scholar · View at PubMed
  190. R. O. Vogel, J. A. M. Smeitink, and L. G. J. Nijtmans, “Human mitochondrial complex I assembly: a dynamic and versatile process,” Biochimica et Biophysica Acta, vol. 1767, no. 10, pp. 1215–1227, 2007. View at Publisher · View at Google Scholar · View at PubMed
  191. N. Vahsen, C. Candé, J.-J. Brière, et al., “AIF deficiency compromises oxidative phosphorylation,” EMBO Journal, vol. 23, no. 23, pp. 4679–4689, 2004. View at Publisher · View at Google Scholar · View at PubMed
  192. K. Bych, S. Kerscher, D. J. A. Netz, et al., “The iron-sulphur protein Ind1 is required for effective complex I assembly,” EMBO Journal, vol. 27, no. 12, pp. 1736–1746, 2008. View at Publisher · View at Google Scholar · View at PubMed
  193. D. Ghezzi, P. Goffrini, G. Uziel, et al., “SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy,” Nature Genetics, vol. 41, no. 6, pp. 654–656, 2009. View at Publisher · View at Google Scholar · View at PubMed
  194. P. de Lonlay, I. Valnot, A. Barrientos, et al., “A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure,” Nature Genetics, vol. 29, no. 1, pp. 57–60, 2001. View at Publisher · View at Google Scholar · View at PubMed
  195. P. Pecinai, H. Houš'ková, H. Hansíková, J. Zeman, and J. Houštěk, “Genetic defects of cytochrome c oxidase assembly,” Physiological Research, vol. 53, supplement 1, pp. S213–S223, 2004.
  196. Z.-G. Wang, P. S. White, and S. H. Ackerman, “Atp11p and Atp12p are assembly factors for the F1-ATPase in human mitochondria,” Journal of Biological Chemistry, vol. 276, no. 33, pp. 30773–30778, 2001. View at Publisher · View at Google Scholar · View at PubMed
  197. X. Zeng, W. Neupert, and A. Tzagoloff, “The metalloprotease encoded by ATP23 has a dual function in processing and assembly of subunit 6 of mitochondrial ATPase,” Molecular Biology of the Cell, vol. 18, no. 2, pp. 617–626, 2007. View at Publisher · View at Google Scholar · View at PubMed
  198. L. Stiburek, D. Fornuskova, L. Wenchich, M. Pejznochova, H. Hansikova, and J. Zeman, “Knockdown of human Oxa1l impairs the biogenesis of F1Fo-ATP synthase and NADH:ubiquinone oxidoreductase,” Journal of Molecular Biology, vol. 374, no. 2, pp. 506–516, 2007. View at Publisher · View at Google Scholar · View at PubMed
  199. N. V. Dudkina, S. Sunderhaus, E. J. Boekema, and H.-P. Braun, “The higher level of organization of the oxidative phosphorylation system: mitochondrial supercomplexes,” Journal of Bioenergetics and Biomembranes, vol. 40, no. 5, pp. 419–424, 2008. View at Publisher · View at Google Scholar · View at PubMed
  200. E. A. Schon and N. A. Dencher, “Heavy breathing: energy conversion by mitochondrial respiratory supercomplexes,” Cell Metabolism, vol. 9, no. 1, pp. 1–3, 2009. View at Publisher · View at Google Scholar · View at PubMed
  201. R. Acín-Pérez, P. Fernández-Silva, M. L. Peleato, A. Pérez-Martos, and J. A. Enriquez, “Respiratory active mitochondrial supercomplexes,” Molecular Cell, vol. 32, no. 4, pp. 529–539, 2008. View at Publisher · View at Google Scholar · View at PubMed
  202. H. Schägger, R. De Coo, M. F. Bauer, S. Hofmann, C. Godino, and U. Brandt, “Significance of respirasomes for the assembly/stability of human respiratory chain complex I,” Journal of Biological Chemistry, vol. 279, no. 35, pp. 36349–36353, 2004. View at Publisher · View at Google Scholar · View at PubMed
  203. M. McKenzie, M. Lazarou, D. R. Thorburn, and M. T. Ryan, “Mitochondrial respiratory chain supercomplexes are destabilized in Barth Syndrome patients,” Journal of Molecular Biology, vol. 361, no. 3, pp. 462–469, 2006. View at Publisher · View at Google Scholar · View at PubMed
  204. H. Chen and D. C. Chan, “Emerging functions of mammalian mitochondrial fusion and fission,” Human Molecular Genetics, vol. 14, no. 2, pp. R283–R289, 2005. View at Publisher · View at Google Scholar · View at PubMed
  205. M. Liesa, M. Palacin, and A. Zorzano, “Mitochondrial dynamics in mammalian health and disease,” Physiological Reviews, vol. 89, no. 3, pp. 799–845, 2009. View at Publisher · View at Google Scholar · View at PubMed
  206. P. A. Parone, S. Da Cruz, D. Tondera, et al., “Preventing mitochondrial fission impairs mitochondrial function and leads to loss of mitochondrial DNA,” PLoS One, vol. 3, no. 9, article e3257, 2008. View at Publisher · View at Google Scholar · View at PubMed
  207. H. R. Waterham, J. Koster, C. W. T. van Roermund, P. A. W. Mooyer, R. J. A. Wanders, and J. V. Leonard, “A lethal defect of mitochondrial and peroxisomal fission,” New England Journal of Medicine, vol. 356, no. 17, pp. 1736–1741, 2007. View at Publisher · View at Google Scholar · View at PubMed
  208. 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, pp. 717–719, 1988.
  209. D. C. Wallace, G. Singh, M. T. Lott, et al., “Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy,” Science, vol. 242, no. 4884, pp. 1427–1430, 1988.
  210. F. Scaglia and L.-J. C. Wong, “Human mitochondrial transfer RNAs: role of pathogenic mutation in disease,” Muscle and Nerve, vol. 37, no. 2, pp. 150–171, 2008. View at Publisher · View at Google Scholar · View at PubMed
  211. C. Florentz, B. Sohm, P. Tryoen-Tóth, J. Pütz, and M. Sissler, “Human mitochondrial tRNAs in health and disease,” Cellular and Molecular Life Sciences, vol. 60, no. 7, pp. 1356–1375, 2003. View at Publisher · View at Google Scholar · View at PubMed
  212. E. Zifa, S. Giannouli, P. Theotokis, C. Stamatis, Z. Mamuris, and C. Stathopoulos, “Mitochondrial tRNA mutations: clinical and functional perturbations,” RNA Biology, vol. 4, no. 1, pp. 38–66, 2007.
  213. S. S. L. Chan and W. C. Copeland, “DNA polymerase gamma and mitochondrial disease: understanding the consequence of POLG mutations,” Biochimica et Biophysica Acta, vol. 1787, no. 5, pp. 312–319, 2009. View at Publisher · View at Google Scholar · View at PubMed
  214. M. J. Longley, S. Clark, C. Y. W. Man, et al., “Mutant POLG2 disrupts DNA polymerase γ subunits and causes progressive external ophthalmoplegia,” American Journal of Human Genetics, vol. 78, no. 6, pp. 1026–1034, 2006. View at Publisher · View at Google Scholar · View at PubMed
  215. J. A. Mayr, O. Merkel, S. D. Kohlwein, et al., “Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation,” American Journal of Human Genetics, vol. 80, no. 3, pp. 478–484, 2007. View at Publisher · View at Google Scholar · View at PubMed
  216. E. Ostergaard, E. Christensen, E. Kristensen, et al., “Deficiency of the α subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion,” American Journal of Human Genetics, vol. 81, no. 2, pp. 383–387, 2007. View at Publisher · View at Google Scholar · View at PubMed
  217. A. Bourdon, L. Minai, V. Serre, et al., “Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion,” Nature Genetics, vol. 39, no. 6, pp. 776–780, 2007. View at Publisher · View at Google Scholar · View at PubMed
  218. K. D. Hauff and G. M. Hatch, “Cardiolipin metabolism and Barth Syndrome,” Progress in Lipid Research, vol. 45, no. 2, pp. 91–101, 2006. View at Publisher · View at Google Scholar · View at PubMed
  219. E. I. Rugarli and T. Langer, “Translating m-AAA protease function in mitochondria to hereditary spastic paraplegia,” Trends in Molecular Medicine, vol. 12, no. 6, pp. 262–269, 2006. View at Publisher · View at Google Scholar · View at PubMed
  220. G. M. C. Janssen, J. A. Maassen, and J. M. W. van Den Ouweland, “The diabetes-associated 3243 mutation in the mitochondrial tRNA(Leu(UUR)) gene causes severe mitochondrial dysfunction without a strong decrease in protein synthesis rate,” Journal of Biological Chemistry, vol. 274, no. 42, pp. 29744–29748, 1999. View at Publisher · View at Google Scholar
  221. M. Toompuu, V. Tiranti, M. Zeviani, and H. T. Jacobs, “Molecular phenotype of the np 7472 deafness-associated mitochondrial mutation in osteosarcoma cell cybrids,” Human Molecular Genetics, vol. 8, no. 12, pp. 2275–2283, 1999. View at Publisher · View at Google Scholar
  222. H. T. Jacobs, “Disorders of mitochondrial protein synthesis,” Human Molecular Genetics, vol. 12, no. 2, pp. R293–R301, 2003.
  223. J. Finsterer, “Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation,” Acta Neurologica Scandinavica, vol. 116, no. 1, pp. 1–14, 2007. View at Publisher · View at Google Scholar · View at PubMed
  224. H. T. Jacobs and I. J. Holt, “The np 3243 MELAS mutation: damned if you aminoacylate, damned if you don't,” Human Molecular Genetics, vol. 9, no. 4, pp. 463–465, 2000.
  225. Y. Kirino, T. Yasukawa, S. Ohta, et al., “Codon-specific translational defect caused by a wobble modification deficiency in mutant tRNA from a human mitochondrial disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 42, pp. 15070–15075, 2004. View at Publisher · View at Google Scholar · View at PubMed
  226. M. P. King, Y. Koga, M. Davidson, and E. A. Schon, “Defects in mitochondrial protein synthesis and respiratory chain activity segregate with the tRNA(Leu(UUR)) mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes,” Molecular and Cellular Biology, vol. 12, no. 2, pp. 480–490, 1992.
  227. J. A. Enriquez, A. Chomyn, and G. Attardi, “MtDNA mutation in MERRF syndrome causes defective aminoacylation of tRNA(Lys) and premature translation termination,” Nature Genetics, vol. 10, no. 1, pp. 47–55, 1995.
  228. G. Xing, Z. Chen, and X. Cao, “Mitochondrial rRNA and tRNA and hearing function,” Cell Research, vol. 17, no. 3, pp. 227–239, 2007. View at Publisher · View at Google Scholar · View at PubMed
  229. E. Cardaioli, M. T. Dotti, G. Hayek, M. Zappella, and A. Federico, “Studies on mitochondrial pathogenesis of Rett syndrome: ultrastructural data from skin and muscle biopsies and mutational analysis at mtDNA nucleotides 10463 and 2835,” Journal of Submicroscopic Cytology and Pathology, vol. 31, no. 2, pp. 301–304, 1999.
  230. R.-H. Hsieh, J.-Y. Li, C.-Y. Pang, and Y.-H. Wei, “A novel mutation in the mitochondrial 16S rRNA gene in a patient with MELAS syndrome, diabetes mellitus, hyperthyroidism and cardiomyopathy,” Journal of Biomedical Science, vol. 8, no. 4, pp. 328–335, 2001. View at Publisher · View at Google Scholar
  231. J. M. Shoffner, M. D. Brown, A. Torroni, et al., “Mitochondrial DNA variants observed in Alzheimer disease and Parkinson disease patients,” Genomics, vol. 17, no. 1, pp. 171–184, 1993. View at Publisher · View at Google Scholar
  232. J. Rozenski, P. F. Crain, and J. A. McCloskey, “The RNA modification database: 1999 update,” Nucleic Acids Research, vol. 27, no. 1, pp. 196–197, 1999. View at Publisher · View at Google Scholar
  233. Y. Bykhovskaya, E. Mengesha, and N. Fischel-Ghodsian, “Pleiotropic effects and compensation mechanisms determine tissue specificity in mitochondrial myopathy and sideroblastic anemia (MLASA),” Molecular Genetics and Metabolism, vol. 91, no. 2, pp. 148–156, 2007. View at Publisher · View at Google Scholar · View at PubMed
  234. S. S. Ashraf, E. Sochacka, R. Cain, R. Guenther, A. Malkiewicz, and P. F. Agris, “Single atom modification (O→S) of tRNA confers ribosome binding,” RNA, vol. 5, no. 2, pp. 188–194, 1999. View at Publisher · View at Google Scholar
  235. C. Yarian, M. Marszalek, E. Sochacka, et al., “Modified nucleoside dependent Watson-Crick and wobble codon binding by tRNA(Lys)(UUU) species,” Biochemistry, vol. 39, no. 44, pp. 13390–13395, 2000. View at Publisher · View at Google Scholar
  236. L. Valente, N. Shigi, T. Suzuki, and M. Zeviani, “The R336Q mutation in human mitochondrial EFTu prevents the formation of an active mt-EFTu·GTP·aa-tRNA ternary complex,” Biochimica et Biophysica Acta, vol. 1792, no. 8, pp. 791–795, 2009. View at Publisher · View at Google Scholar · View at PubMed
  237. K. A. Dittmar, J. M. Goodenbour, and T. Pan, “Tissue-specific differences in human transfer RNA expression,” PLoS Genetics, vol. 2, no. 12, article e221, 2006. View at Publisher · View at Google Scholar · View at PubMed
  238. A. Tzagoloff and A. Shtanko, “Mitochondrial and cytoplasmic isoleucyl-, glutamyl- and arginyl-tRNA synthetases of yeast are encoded by separate genes,” European Journal of Biochemistry, vol. 230, no. 2, pp. 582–586, 1995. View at Publisher · View at Google Scholar
  239. A. Arnoldi, A. Tonelli, F. Crippa, et al., “A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia,” Human Mutation, vol. 29, no. 4, pp. 522–531, 2008. View at Publisher · View at Google Scholar · View at PubMed
  240. L. Atorino, L. Silvestri, M. Koppen, et al., “Loss of m-AAA protease in mitochondria causes complex I deficiency and increased sensitivity to oxidative stress in hereditary spastic paraplegia,” Journal of Cell Biology, vol. 163, no. 4, pp. 777–787, 2003. View at Publisher · View at Google Scholar · View at PubMed
  241. P. A. Wilkinson, A. H. Crosby, C. Turner, et al., “A clinical, genetic and biochemical study of SPG7 mutations in hereditary spastic paraplegia,” Brain, vol. 127, no. 5, pp. 973–980, 2004. View at Publisher · View at Google Scholar · View at PubMed
  242. M. Koppen, M. D. Metodiev, G. Casari, E. I. Rugarli, and T. Langer, “Variable and tissue-specific subunit composition of mitochondrial m-AAA protease complexes linked to hereditary spastic paraplegia,” Molecular and Cellular Biology, vol. 27, no. 2, pp. 758–767, 2007. View at Publisher · View at Google Scholar · View at PubMed
  243. V. Tiranti, P. D'Adamo, E. Briem, et al., “Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein,” American Journal of Human Genetics, vol. 74, no. 2, pp. 239–252, 2004. View at Publisher · View at Google Scholar · View at PubMed
  244. W. J. Ansorge, “Next-generation DNA sequencing techniques,” New Biotechnology, vol. 25, no. 4, pp. 195–203, 2009. View at Publisher · View at Google Scholar · View at PubMed
  245. T. Tucker, M. Marra, and J. M. Friedman, “Massively parallel sequencing: the next big thing in genetic medicine,” American Journal of Human Genetics, vol. 85, no. 2, pp. 142–154, 2009. View at Publisher · View at Google Scholar · View at PubMed
  246. S. B. Ng, E. H. Turner, P. D. Robertson, et al., “Targeted capture and massively parallel sequencing of 12 human exomes,” Nature, vol. 461, no. 7261, pp. 272–276, 2009. View at Publisher · View at Google Scholar · View at PubMed
  247. G. J. Porreca, K. Zhang, J. B. Li, et al., “Multiplex amplification of large sets of human exons,” Nature Methods, vol. 4, no. 11, pp. 931–936, 2007. View at Publisher · View at Google Scholar · View at PubMed
  248. B. Lehner, C. Crombie, J. Tischler, A. Fortunato, and A. G. Fraser, “Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways,” Nature Genetics, vol. 38, no. 8, pp. 896–903, 2006. View at Publisher · View at Google Scholar · View at PubMed
  249. S. DiMauro and M. Mancuso, “Mitochondrial diseases: therapeutic approaches,” Bioscience Reports, vol. 27, no. 1–3, pp. 125–137, 2007. View at Publisher · View at Google Scholar · View at PubMed
  250. S. Koene and J. Smeitink, “Mitochondrial medicine: entering the era of treatment,” Journal of Internal Medicine, vol. 265, no. 2, pp. 193–209, 2009. View at Publisher · View at Google Scholar · View at PubMed