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Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 7202589, 11 pages
https://doi.org/10.1155/2017/7202589
Research Article

Combined Respiratory Chain Deficiency and UQCC2 Mutations in Neonatal Encephalomyopathy: Defective Supercomplex Assembly in Complex III Deficiencies

1Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
2Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, 8010 Graz, Austria
3Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany
4Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany
5Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8010 Graz, Austria
6Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, 8010 Graz, Austria
7Department of Human Genetics, Medical University of Graz, 8010 Graz, Austria
8Laura Bassi Centre of Expertise-THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, 5020 Salzburg, Austria
9Department for Paediatric and Adolescent Medicine, Schwabing Hospital, Technische Universität München, 80804 Munich, Germany

Correspondence should be addressed to René G. Feichtinger

Received 26 January 2017; Revised 22 March 2017; Accepted 4 June 2017; Published 19 July 2017

Academic Editor: Maik Hüttemann

Copyright © 2017 René G. Feichtinger 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. O. Barel, Z. Shorer, H. Flusser et al., “Mitochondrial complex III deficiency associated with a homozygous mutation in UQCRQ,” American Journal of Human Genetics, vol. 82, no. 5, pp. 1211–1216, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. P. Gaignard, M. Menezes, M. Schiff et al., “Mutations in CYC1, encoding cytochrome c1 subunit of respiratory chain complex III, cause insulin-responsive hyperglycemia,” American Journal of Human Genetics, vol. 93, no. 2, pp. 384–389, 2013. View at Publisher · View at Google Scholar · View at Scopus
  3. G. Gasparre, E. Hervouet, E. de Laplanche et al., “Clonal expansion of mutated mitochondrial DNA is associated with tumor formation and complex I deficiency in the benign renal oncocytoma,” Human Molecular Genetics, vol. 17, no. 7, pp. 986–995, 2008. View at Publisher · View at Google Scholar · View at Scopus
  4. F. Invernizzi, M. Tigano, C. Dallabona et al., “A homozygous mutation in LYRM7/MZM1L associated with early onset encephalopathy, lactic acidosis, and severe reduction of mitochondrial complex III activity,” Human Mutation, vol. 34, no. 12, pp. 1619–1622, 2013. View at Publisher · View at Google Scholar · View at Scopus
  5. J. Koch, P. Freisinger, R. G. Feichtinger et al., “Mutations in TTC19: expanding the molecular, clinical and biochemical phenotype,” Orphanet Journal of Rare Diseases, vol. 10, no. 1, p. 40, 2015. View at Publisher · View at Google Scholar · View at Scopus
  6. N. Miyake, S. Yano, C. Sakai et al., “Mitochondrial complex III deficiency caused by a homozygous UQCRC2 mutation presenting with neonatal-onset recurrent metabolic decompensation,” Human Mutation, vol. 34, no. 3, pp. 446–452, 2013. View at Publisher · View at Google Scholar · View at Scopus
  7. E. J. Tucker, B. F. Wanschers, R. Szklarczyk et al., “Mutations in the UQCC1-interacting protein, UQCC2, cause human complex III deficiency associated with perturbed cytochrome b protein expression,” PLoS Genetics, vol. 9, no. 12, article e1004034, 2013. View at Publisher · View at Google Scholar · View at Scopus
  8. B. F. Wanschers, R. Szklarczyk, M. A. van den Brand et al., “A mutation in the human CBP4 ortholog UQCC3 impairs complex III assembly, activity and cytochrome b stability,” Human Molecular Genetics, vol. 23, no. 23, pp. 6356–6365, 2014. View at Publisher · View at Google Scholar · View at Scopus
  9. F. A. Zimmermann, J. A. Mayr, D. Neureiter et al., “Lack of complex I is associated with oncocytic thyroid tumours,” British Journal of Cancer, vol. 100, no. 9, pp. 1434–1437, 2009. View at Publisher · View at Google Scholar · View at Scopus
  10. L. S. Kremer, C. L’Hermitte-Stead, P. Lesimple et al., “Severe respiratory complex III defect prevents liver adaptation to prolonged fasting,” Journal of Hepatology, vol. 65, no. 2, pp. 377–385, 2016. View at Publisher · View at Google Scholar · View at Scopus
  11. L. Cambier, P. Rassam, B. Chabi et al., “M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic beta-cells through modulation of respiratory chain activity,” PloS One, vol. 7, no. 2, article e31815, 2012. View at Publisher · View at Google Scholar · View at Scopus
  12. M. Sumitani, K. Kasashima, E. Ohta, D. Kang, and H. Endo, “Association of a novel mitochondrial protein M19 with mitochondrial nucleoids,” Journal of Biochemistry, vol. 146, no. 5, pp. 725–732, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. J. A. Letts, K. Fiedorczuk, and L. A. Sazanov, “The architecture of respiratory supercomplexes,” Nature, vol. 537, no. 7622, pp. 644–648, 2016. View at Publisher · View at Google Scholar · View at Scopus
  14. L. S. Kremer, K. Danhauser, D. Herebian et al., “NAXE mutations disrupt the cellular NAD(P)HX repair system and cause a lethal neurometabolic disorder of early childhood,” American Journal of Human Genetics, vol. 99, no. 4, pp. 894–902, 2016. View at Publisher · View at Google Scholar · View at Scopus
  15. H. Li and R. Durbin, “Fast and accurate short read alignment with burrows-wheeler transform,” Bioinformatics, vol. 25, no. 14, pp. 1754–1760, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. H. Li, B. Handsaker, A. Wysoker et al., “The sequence alignment/map format and SAMtools,” Bioinformatics, vol. 25, no. 16, pp. 2078-2079, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. R. G. Feichtinger, S. Weis, J. A. Mayr et al., “Alterations of oxidative phosphorylation complexes in astrocytomas,” Glia, vol. 62, no. 4, pp. 514–525, 2014. View at Publisher · View at Google Scholar · View at Scopus
  18. R. G. Feichtinger, F. Zimmermann, J. A. Mayr et al., “Low aerobic mitochondrial energy metabolism in poorly- or undifferentiated neuroblastoma,” BMC Cancer, vol. 10, p. 149, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. J. A. Mayr, J. Paul, P. Pecina et al., “Reduced respiratory control with ADP and changed pattern of respiratory chain enzymes as a result of selective deficiency of the mitochondrial ATP synthase,” Pediatric Research, vol. 55, no. 6, pp. 988–994, 2004. View at Publisher · View at Google Scholar · View at Scopus
  20. I. Wittig, H. P. Braun, and H. Schagger, “Blue native PAGE,” Nature Protocols, vol. 1, no. 1, pp. 418–428, 2006. View at Publisher · View at Google Scholar · View at Scopus
  21. E. Fernandez-Vizarra and M. Zeviani, “Nuclear gene mutations as the cause of mitochondrial complex III deficiency,” Frontiers in Genetics, vol. 6, p. 134, 2015. View at Publisher · View at Google Scholar · View at Scopus
  22. S. Haut, M. Brivet, G. Touati et al., “A deletion in the human QP-C gene causes a complex III deficiency resulting in hypoglycaemia and lactic acidosis,” Human Genetics, vol. 113, no. 2, pp. 118–122, 2003. View at Publisher · View at Google Scholar
  23. M. Morán, L. Marín‐Buera, M. C. Gil‐Borlado et al., “Cellular pathophysiological consequences of BCS1L mutations in mitochondrial complex III enzyme deficiency,” Human Mutation, vol. 31, no. 8, pp. 930–941, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. C. Dallabona, T. E. Abbink, R. Carrozzo et al., “LYRM7 mutations cause a multifocal cavitating leukoencephalopathy with distinct MRI appearance,” Brain, vol. 139, Part 3, pp. 782–794, 2016. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Babot, A. Birch, P. Labarbuta, and A. Galkin, “Characterisation of the active/de-active transition of mitochondrial complex I,” Biochimica et Biophysica Acta, vol. 1837, no. 7, pp. 1083–1092, 2014. View at Google Scholar
  26. M. Hüttemann, I. Lee, L. I. Grossman, J. W. Doan, and T. H. Sanderson, “Phosphorylation of mammalian cytochrome c and cytochrome c oxidase in the regulation of cell destiny: respiration, apoptosis, and human disease,” Advances in Experimental Medicine and Biology, vol. 748, pp. 237–264, 2012. View at Publisher · View at Google Scholar · View at Scopus
  27. G. Mahapatra, A. Varughese, Q. Ji et al., “Phosphorylation of cytochrome c threonine 28 regulates electron transport chain activity in kidney: implications for AMP kinase,” The Journal of Biological Chemistry, vol. 292, no. 1, pp. 64–79, 2017. View at Publisher · View at Google Scholar
  28. T. H. Sanderson, G. Mahapatra, P. Pecina et al., “Cytochrome C is tyrosine 97 phosphorylated by neuroprotective insulin treatment,” PloS One, vol. 8, no. 11, article e78627, 2013. View at Publisher · View at Google Scholar · View at Scopus
  29. R. Acı́n-Pérez, M. P. Bayona-Bafaluy, P. Fernández-Silva et al., “Respiratory complex III is required to maintain complex I in mammalian mitochondria,” Molecular Cell, vol. 13, no. 6, pp. 805–815, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. J. A. Mayr, D. Meierhofer, F. Zimmermann et al., “Loss of complex I due to mitochondrial DNA mutations in renal oncocytoma,” Clinical Cancer Research, vol. 14, no. 8, pp. 2270–2275, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. F. A. Zimmermann, J. A. Mayr, R. Feichtinger et al., “Respiratory chain complex I is a mitochondrial tumor suppressor of oncocytic tumors,” Frontiers in Bioscience, vol. 3, pp. 315–325, 2011. View at Google Scholar
  32. H. Schägger, R. de Coo, M. F. Bauer, S. Hofmann, C. Godinot, and U. Brandt, “Significance of respirasomes for the assembly/stability of human respiratory chain complex I,” The Journal of Biological Chemistry, vol. 279, no. 35, pp. 36349–36353, 2004. View at Publisher · View at Google Scholar · View at Scopus
  33. W. Suthammarak, P. G. Morgan, and M. M. Sedensky, “Mutations in mitochondrial complex III uniquely affect complex I in Caenorhabditis elegans,” The Journal of Biological Chemistry, vol. 285, no. 52, pp. 40724–40731, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. P. Gaignard, D. Eyer, E. Lebigot et al., “UQCRC2 mutation in a patient with mitochondrial complex III deficiency causing recurrent liver failure, lactic acidosis and hypoglycemia,” Journal of Human Genetics, vol. 62, no. 7, pp. 729–731, 2017. View at Publisher · View at Google Scholar
  35. R. Pérez-Pérez, T. Lobo-Jarne, D. Milenkovic et al., “COX7A2L is a mitochondrial complex III binding protein that stabilizes the III2+IV supercomplex without affecting respirasome formation,” Cell Reports, vol. 16, no. 9, pp. 2387–2398, 2016. View at Publisher · View at Google Scholar · View at Scopus
  36. S. Cogliati, E. Calvo, M. Loureiro et al., “Mechanism of super-assembly of respiratory complexes III and IV,” Nature, vol. 539, no. 7630, pp. 579–582, 2016. View at Publisher · View at Google Scholar
  37. T. Hayashi, Y. Asano, Y. Shintani et al., “Higd1a is a positive regulator of cytochrome c oxidase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 5, pp. 1553–1558, 2015. View at Publisher · View at Google Scholar · View at Scopus
  38. F. N. Gellerich, J. A. Mayr, S. Reuter, W. Sperl, and S. Zierz, “The problem of interlab variation in methods for mitochondrial disease diagnosis: enzymatic measurement of respiratory chain complexes,” Mitochondrion, vol. 4, no. 5-6, pp. 427–439, 2004. View at Publisher · View at Google Scholar · View at Scopus
  39. E. L. Blakely, A. L. Mitchell, N. Fisher et al., “A mitochondrial cytochrome b mutation causing severe respiratory chain enzyme deficiency in humans and yeast,” The FEBS Journal, vol. 272, no. 14, pp. 3583–3592, 2005. View at Publisher · View at Google Scholar · View at Scopus