Depletion of mitochondrial DNA in fibroblast cultures from patients with POLG1 mutations is a consequence of catalytic mutations

Human Molecular Genetics

Volumn 17, Issue 16, 2008, Pages 2496-2506

  Ashley, Neil ^a   O'Rourke, Anthony ^b   Smith, Conrad ^b   Adams, Susan ^b   Gowda, Vasantha ^a   Zeviani, Massimo ^c   Brown, Garry K ^a   Fratter, Carl ^b   Poulton, Joanna ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b CHURCHILL HOSPITAL   (United Kingdom)

^c DEPARTMENT OF NEUROSURGERY   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME C OXIDASE; DNA POLYMERASE; EXONUCLEASE; MITOCHONDRIAL DNA; PROTEIN POLG1; SUCCINATE DEHYDROGENASE;

ADOLESCENT; ALLELE; ALPERS DISEASE; ARTICLE; AUTOSOMAL RECESSIVE INHERITANCE; CATALYSIS; CHILD; CLINICAL ARTICLE; CLINICAL FEATURE; CONTROLLED STUDY; DISEASE SEVERITY; ENZYME ACTIVITY; FEMALE; FIBROBLAST; GENE MUTATION; GENETIC ANALYSIS; GENOTYPE; GENOTYPE PHENOTYPE CORRELATION; HEPATIC ENCEPHALOPATHY; HETEROZYGOTE; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; INFANT; LIFE EXPECTANCY; MALE; MISSENSE MUTATION; NONSENSE MUTATION; NUCLEOTIDE SEQUENCE; PHENOTYPE; PRIORITY JOURNAL;

ADOLESCENT; CELLS, CULTURED; CHILD; CHILD, PRESCHOOL; DIFFUSE CEREBRAL SCLEROSIS OF SCHILDER; DNA, MITOCHONDRIAL; DNA-DIRECTED DNA POLYMERASE; FEMALE; FIBROBLASTS; GENOTYPE; HUMANS; INFANT; LIFE EXPECTANCY; MALE; MITOCHONDRIA; MUTATION; PHENOTYPE; PROTEIN STRUCTURE, TERTIARY; RETROSPECTIVE STUDIES;

EUKARYOTA;

EID: 48249120297     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddn150     Document Type: Article

References (45)

1. Moraes, C.T., Shanske, S., Tritschler, H.J., Aprille, J.R., Andreetta, F., Bonilla, E., Schon, E.A. and DiMauro, S. (1991) mtDNA depletion with variable tissue expression: A novel genetic abnormality in mitochondrial diseases. Am. J. Hum. Genet., 48, 492-501.
2. Moraes, C., Ricci, E., Arnaudo, E., Bonilla, E., DiMauro, S. and Schon, E. (1993) Quantitative defects of mitochondrial DNA. In DiMauro, S. and Wallace, D. (eds), Mitochondrial DNA in Human Pathology. Raven, New York, pp. 97-108.
3. Barthelemy, C., de Baulny, H.O. and Lombes, A. (2002) D-loop mutations in mitochondrial DNA: Link with mitochondrial DNA depletion? Hum. Genet., 110, 479-487.
4. Taanman, J.W., Bodnar, A.G., Cooper, J.M., Morris, A.A., Clayton, P.T., Leonard, J.V. and Schapira, A.H. (1997) Molecular mechanisms in mitochondrial DNA depletion syndrome. Hum. Mol. Genet., 6, 935-942.
5. Blake, J.C., Taanman, JW., Morris, A.M., Gray, R.G., Cooper, J.M., McKiernan, P.J., Leonard, J.V. and Schapira, A.H. (1999) Mitochondrial DNA depletion syndrome is expressed in amniotic fluid cell cultures. Am. J. Pathol., 155, 67-70.
6. Bodnar, A.G., Cooper, J.M., Holt, I.J., Leonard, J.V. and Schapira, A.H. (1993) Nuclear complementation restores mtDNA levels in cultured cells from a patient with mtDNA depletion. Am. J. Hum. Genet., 53, 663-669.
7. Saada, A., Shaag, A. and Elpeleg, O. (2003) mtDNA depletion myopathy: elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiency. Mol. Genet. Metab., 79, 1-5.
8. Spinazzola, A. and Zeviani, M. (2005) Disorders of nuclear-mitochondrial intergenomic signaling. Gene, 354, 162-168.
9. Suomalainen, A. and Kaukonen, J. (2001) Diseases caused by nuclear genes affecting mtDNA stability. Am. J. Med. Genet., 106, 53-61.
10. Naviaux, R.Y- and Nguyen, K.V. (2004) POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. Ann. Neurol., 55, 706-712.
11. Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M. et al. (2001) The deoxyguanosine kmase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Nat. Genet., 29, 337-341.
12. Spinazzola, A., Viscomi, C., Fernandez-Vizarra, E., Carrara, F., D'Adamo, P., Calvo, S., Marsano, R.M., Donnini, C., Weiher, H., Strisciuglio, P. et al. (2006) MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion. Nat. Genet., 38, 570-575.
13. Hakonen, A.H., Isohanni, P., Paetau, A., Herva, R., Suomalainen, A. and Lonnqvist, T. (2007) Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion. Brain, 130, 3032-3040.
14. Ostergaard, E., Christensen, E., Kristensen, E., Mogensen, B., Duno, M., Shoubridge, E.A. and Wibrand, F. (2007) Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion. Am. J. Hum. Genet., 81, 383-387.
15. Elpeleg, O., Miller, C., Hershkovitz, E., Bitner-Glindzicz, M., Bondi-Rubinstein, G., Rahman, S., Pagnamenta, A., Eshhar, S. and Saada, A. (2005) Deficiency of the ADP-Forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion. Am. J Hum. Genet., 76, 1081-1086.
16. Bourdon, A., Minai, L., Serre, V., Jais, J.P., Sarzi, E., Aubert, S., Chretien, D., de Lonlay, P., Paquis-Flucklinger, V., Arakawa, H. et al. (2007) Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochandrial DNA depletion. Nat. Genet., 39, 776-780.
17. Nishino, L, Spinazzola, A. and Hirano, M. (1999) Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science, 283, 689-692.
18. Barthelemy, C., Ogier de Baulny, H., Diaz, J., Cheval, M.A., Fraction, P., Romero, N., Goutieres, F., Fardeau, M. and Lombes, A. (2001) Late-onset mitochondrial DNA depletion: DNA copy number, multiple deletions, and compensation. Ann. Neurol., 49, 607-617.
19. Chinnery, P.F. and Zeviani, M. (2007) 155th ENMC workshop: Polymerase gamma and disorders of mitochondrial DNA synthesis, 21-23 September 2007, Naarden, The Netherlands. Neuromuscul. Disord., 18, 259-267.
20. Hakonen, A.H., Heiskanen, S., Juvonen, V., Lappalainen, I., Luoma, P.T., Rantamaki, M., Goethem, G.V., Lofgren, A., Hackman, P., Paetau, A. et al. (2005) Mitochondrial DNA polymerase W748S mutation: A common cause of autosomal recessive ataxia with ancient European origin. Am. J. Hum. Genet., 77, 430-441.
21. Chan, S.S., Longley, M.J., Naviaux, R.K. and Copeland, W.C. (2005) Mono-allelic POLG expression resulting from nonsense-mediated decay and alternative splicing in a patient with Alpers syndrome. DNA Repair (Amst), 4, 1381-1389.
22. Harding, B.N., Alsanjari, N., Smith, S.J., Wiles, C.M., Thrush, D., Miller, D.H., Scaravilli, F. and Harding, A.E. (1995) Progressive neuronal degeneration of childhood with liver disease (Alpers' disease) presenting in young adults. J. Neurol. Neurosurg. Psychiatry, 58, 320-325.
23. Ashley, N., Harris, D. and Poulton, J. (2005) Detection of mitochondrial DNA depletion in living human cells using PicoGreen staining. Exp. Cell Res., 303, 432-446.
24. Ashley, N., Adams, S., Slama, A., Zeviani, M., Suomalainen, A., Andreu, A., Naviaux, R. and Poulton, J. (2007) Defects in maintenance of mitochondrial DNA are associated with intramitochondrial nucleotide imbalances. Hum. Mol. Genet., 16, 1400-1411.
25. Morten, K.J., Ashley, N., Wijburg, F., Hadzic, N., Parr, J., Jayawant, S., Adams, S., Bindoff, L., Bakker, H.D., Mieli-Vergani, G. et al. (2007) Liver mtDNA content increases during development: A comparison of methods and the importance of age- and tissue-specific controls for the diagnosis of mtDNA depletion. Mitochondrion, 16, 1400-1411.
26. Van Goethem, G., Luoma, P., Rantamaki, M., Al Memar, A., Kaakkola, S., Hackman, P., Krahe, R., Lofgren, A., Martin, J.J., De Jonghe, P. et al. (2004) POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement. Neurology, 63, 1251-1257.
27. Tzoulis, C., Engelsen, B.A., Telstad, W., Aasly, J., Zeviani, M., Winterthun, S., Ferrari, G., Aarseth, J.H. and Bindoff, L.A. (2006) The spectrum of clinical disease caused by the A467T and W748S POLG mutations: A study of 26 cases. Brain, 129, 1685-1692.
28. Gonzalez-Vioque, E., Blazquez, A., Fernandez-Moreira, D., Bornstein, B., Bautista, J., Arpa, J., Navarro, C., Campos, Y., Fernandez-Moreno, M.A., Garesse, R. et al. (2006) Association of novel POLG mutations and multiple mitochondrial DNA deletions with variable clinical phenotypes in a Spanish population. Arch. Neurol., 63, 107-111.
29. Stuart, G.R., Santos, J.H., Strand, M.K., Van Houten, B. and Copeland, W.C. (2006) Mitochondrial and nuclear DNA defects in Saccharomyces cerevisiae with mutations in DNA polymerase {gamma} associated with progressive external ophthalmoplegia. Hum. Mol. Genet., 15, 363-374.
30. Vila, M.R., Segovia-Silvestre, T., Gamez, J., Marina, A., Naini, A.B., Meseguer, A., Lombes, A., Bonilla, E., DiMauro, S., Hirano, M. et al. (2003) Reversion of mtDNA depletion in a patient with TK2 deficiency. Neurology, 60, 1203-1205.
31. Ducluzeau, P.H., Lachaux, A., Bouvier, R., Duborjal, H., Stepien, G., Bozon, D. and Mousson de Camaret, B. (2002) Progressive reversion of clinical and molecular phenotype in a child with liver mitochondrial DNA depletion. J. Repatol., 36, 698-703.
32. Chan, S.S., Longley, M.J. and Copeland, W.C. (2006) Modulation of the W748S mutation in DNA polymerase {gamma} by the E1143G polymorphism in mitochondrial disorders. Hum. Mol. Genet., 15, 3473-3483.
33. Hudson, G. and Chinnery, P.F. (2006) Mitochondrial DNA polymerase-gamma and human disease. Hum. Mol. Genet., 15 (Spec no. 2), R244-R252.
34. Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J.N., Rovio, A.T., Bruder, C.E., Bohlooly, Y.M., Gidlof, S., Oldfors, A., Wibom, R. et al. (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature, 429, 417-423.
35. Graziewicz, M.A., Bienstock, R.J. and Copeland, W.C. (2007) The DNA polymerase gamma Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-2′-deoxyguanosine. Hum. Mol. Genet., 16, 2729-2739.
36. Trifunovic, A., Hansson, A., Wredenberg, A., Rovio, A.T., Dufour, E., Khvorostov, I., Spelbrink, J.N., Wibom, R., Jacobs, H.T. and Larsson, N.G. (2005) Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc. Natl Acad. Sci. USA, 102, 17993-17998.
37. Lewin, B. (2004) DNA replication: In G, Carson. (ed), Genes VIII, Pearson Education International, pp. 387-392.
38. Horvath, R., Hudson, G., Ferrari, G., Futterer, N., Ahola, S., Lamantea, E., Prokisch, H., Lochmuller, H., McFarland, R., Ramesh, V. et al. (2006) Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene. Brain, 129, 1674-1684.
39. Ferrari, G., Lamantea, E., Donati, A., Filosto, M., Briem, E., Carrara, F., Parini, R., Simonati, A., Santer, R. and Zeviani, M. (2005) Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-gammaA. Brain, 128, 723-731.
40. Alberio, S., Mineri, R., Tiranti, V. and Zeviani, M. (2007) Depletion of mtDNA: Syndromes and genes. Mitochondrion, 7, 6-12.
41. Wanrooij, S., Goffart, S., Pohjoismaki, J.L., Yasukawa, T. and Spelbrink, J.N. (2007) Expression of catalytic mutants of the mtDNA helicase Twinkle and polymerase POLG causes distinct replication stalling phenotypes. Nucleic Acids Res., 35, 3238-3251.
42. Taamnan, JW., Muddle, J.R. and Muntau, A.C. (2003) Mitochondrial DNA depletion can be prevented by dGMP and dAMP supplementation in a resting culture of deoxyguanosine kinase-deficient fibroblasts. Hum Mol. Genet., 12, 1839-1845.
43. Baruffini, E., Lodi, T., Dallabona, C., Puglisi, A., Zeviani, M. and Ferrero, I. (2006) Genetic and chemical rescue of the Saccharomyces cerevisiae phenotype induced by mitochondrial DNA polymerase mutations associated with progressive external oplithalmoplegia in humans. Hum. Mot. Genet., 15, 2846-2955.
44. Magnusson, J., Orth, M., Lestienne, P. and Taamnan, J.W. (2003) Replication of mitochondrial DNA occurs throughout the mitochondria of cultured human cells. Exp. Cell Res., 289, 133-142.
45. Elson, J.L., Samuels, D.C., Johnson, M.A., Turnbull, D.M. and Chinnery, P.F. (2002) The length of cytochrome c oxidase-negative segments in muscle fibres in patients with mtDNA myopathy. Neuromuscul. Disord. 12, 858-864.