Heterogeneity of mitochondrial diseases caused by defects in mitochondrial respiratory chain complex I
Abstract
The common cause of mitochondrial diseases is hereditary defects in mitochondrial respiratory chain complex I, which account for about 30% of the cases of mitochondrial diseases in children. Complex I is the largest and most complicated enzyme complex of the respiratory electron chain. The function of Complex I is controlled by both nuclear and mitochondrial genomes and it seems to be determined by at least 300 genes. Complex I is comprised of 45 subunits: 7 of them are encoded by mitochondrial DNA, the others are by nuclear DNA. Besides, there are additional factors that are located outside Complex I, but determine its stability and activity. The paper analyzes the clinical forms of Complex I deficiency-induced diseases; the most common of them is Leigh syndrome. The diseases are generally characterized by an early onset, severe involvement of the nervous, muscular, and cardiovascular systems. If the treatment is ineffective, it is particularly important to identify a gene mutation to verify the diagnosis, as well as antenatal diagnosis.
About the Author
E. A. Nikolaeva
Research Clinical Institute of Pediatrics, N.I. Pirogov Russian National Research Medical University, Moscow
Russian Federation
Russian Federation
References
1. Schaefer A.M., McFarland R., Blakely E.L. et al. Prevalence of mitochondrial DNA disease in adults. Ann Neurol 2008; 63: 35–39.
2. Skladal D., Halliday J., Thorburn D.R. Minimum birth prevalence of mitochondrial respiratory chain disorders in children. Brain 2003; 126: Pt 8: 1905–1912.
3. Bernier F.P., Boneh A., Dennett X. et al. Diagnostic criteria for respiratory chain disorders in adults and children. Neurology 2002; 59: 1406–1411.
4. Wolf N.I., Smeitink A.M. Mitochondrial disorders: а proposal for consensus diagnostic criteria in infants and children. Neurology 2002; 59: 1402–1405.
5. Zeviani M., Carelli V. Mitochondrial disorders. Curr Opin Neurol 2003; 16: 585–594.
6. Finsterer J. Overview on visceral manifestations of mitochondrial disorders. Neth J Med 2006; 64: 3: 61–71.
7. Haas R.H., Parikh S., Falk M.J. et al. The in-depth evaluation of suspected mitochondrial disease. Mol Genet Metab 2008; 94: 1: 16–37.
8. Shchelochkov O.A.. Li F.Y., Wang J. et al. Milder clinical course of type IV 3-methylglutaconic aciduria due to a novel mutation in TMEM70. Mol Genet Metab 2010; 101: 2–3: 282–285.
9. Loeffen J.L., Smeitink J.A., Trijbels J.M. et al. Isolated complex I deficiency in children: clinical, biochemical and genetic aspects. Hum Mutat 2000; 15: 123–134.
10. Bйnit P., Chretien D., Kadhom N. et al. Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency. Am J Hum Genet 2001; 68: 6: 1344–1352.
11. Distelmaier F., Koopman W.J., van der Heuvel L.P. et al. Mitochondrial complex I deficiency: from organell dysfunction to clinical disease. Brain 2009; 132: 833–842.
12. Goldstein A.C., Bhatia P., Vento J.M. Mitochondrial Disease in Childhood: Nuclear Encoded. Neurotherapeutics 2013; 10: 2: 212–226.
13. Rahman S., Thorburn D.R. 189th ENMC International workshop Complex I deficiency: Diagnosis and treatment. 20–22 April 2012, Naarden, The Netherlands. Neuromuscular Disorders 2013; 23: 6: 506–515.
14. Гривенникова В.Г., Виноградов А.Д. Митохондриаль- ный комплекс 1. Успехи биологической химии 2003; 43: 19–58. (Grivennikova V.G., Vinogradov А.D. Mitochondrial complex I. Uspekhi biologicheskoj khimii 2003; 43: 19–58.)
15. Carroll J., Fearnley I.M., Skehel J.M. et al. Bovine complex I is a complex of 45 different subunits. J Biol Chem 2006; 281: 32724–32727.
16. Angerer H., Zwicker K., Wumaier Z. et al. A scaffold of accessory subunits links the peripheral arm and the distal protonpumping module of mitochondrial complex I. Biochem J 2011; 437: 279–288.
17. Calvo S.E., Tucker E.J., Compton A.G. et al. High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency. Nat Genet 2010; 42: 10: 851–858.
18. Pagniez-Mammeri H., Loublier S., Legrand A. et al. Mitochondrial complex I deficiency of nuclear origin I. Structural genes. Mol Genet Metab 2012; 105: 2: 163–172.
19. Lazaroua M., Thorburnb D.R., Ryana M.T., McKenziea M. Assembly of mitochondrial complex I and defects in disease. Biochim Biophys Acta 2009; 1793: 1: 78–88.
20. Janssen R., Smeitink J., Smeets R., van Den Heuvel L. CIA30 complex I assembly factor: a candidate for human complex I deficiency? Hum Genet 2002; 110: 264–270.
21. Ogilvie I., Kennaway N.G., Shoubridge E.A. A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy. J Clin Invest 2005; 115: 2784– 2792.
22. Vogel R.O., Smeitink J.A., Nijtmans L.G. Human mitochondrial complex I assembly: a dynamic and versatile process. Biochim Biophys Acta 2007; 1767: 1215–1227.
23. Pagniez-Mammeri H., Rak M., Legrand A. et al. Mitochondrial complex I deficiency of nuclear origin II. Non-structural genes. Mol Genet Metab 2012; 105: 2: 173–179.
24. Di Mauro S., Davidzon G. Mitochondrial DNA and disease. Ann Med 2005; 37: 222–232.
25. Nouws J., Nijtmans L., Smeitink J.A. et al. Assembly factors as a new class of disease genes for mitochondrial complex I deficiency: cause, pathology and treatment options. Brain 2011; 135: 1: 12–22.
26. Kirby D.M., Salemi R., Sugiana C. et al. NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency. J Clin Invest 2004; 114: 6: 837–845.
27. Swalwell H., Kirby D.M., Blakely E.L. Respiratory chain complex I deficiency caused by mitochondrial DNA mutations Eur J Hum Genet 2011; 19: 7: 769–775.
28. Koene S., Rodenburg R.J., van der Knaap M.S. et al. Natural disease course and genotype-phenotype correlations in Complex I deficiency caused by nuclear gene defects: what we learned from 130 cases. Inherit Metab Dis 2012; 35: 5: 737–747.
29. Sarzi E., Brown M.D., Lebon S. et al. A novel recurrent mitochondrial DNA mutation in ND3 gene is associated with isolated complex I deficiency causing Leigh syndrome and dystonia. Am J Med Genet 2007; 143A: 33–41.
30. Finsterer J., Melichart M., Wцhrer A. Complex-I defect with minimal manifestations. Arch Med Sci 2014; 10: 1: 200–202
31. Haack T.B., Haberberger B., Frisch E.M. et al. Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing. J Med Genet 2012; 49: 4: 277–283.
32. Kevelam S.H., Rodenburg R.J., Wolf N.I. et al. NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern. Neurology 2013; 80: 17: 1577–1583.
33. Kanabus M., Heales S. J., Rahman S. Development of pharmacological strategies for mitochondrial disorders Br J Pharmacol 2014; 171: 8: 1798–1817.
34. Gerards M., van den Bosch B.J., Danhauser K. et al. Riboflavin- responsive oxidative phosphorylation complex I deficiency caused by defective ACAD9: new function for an old gene. Brain 2011; 134: 210–219.
Review
For citations:
Nikolaeva E.A. Heterogeneity of mitochondrial diseases caused by defects in mitochondrial respiratory chain complex I. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2015;60(3):21-25. (In Russ.)
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