Limited dCTP availability accounts for mitochondrial DNA depletion in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)

PLoS Genetics

Volumn 7, Issue 3, 2011, Pages

  González Vioque, Emiliano ^a,b   Torres Torronteras, Javier ^a,b   Andreu, Antoni L ^a,b   Martí, Ramon ^a,b  

^a HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

^b CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED DE ENFERMEDADES RARAS CIBERER   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

DEOXYADENOSINE TRIPHOSPHATE; DEOXYCYTIDINE TRIPHOSPHATE; DEOXYGUANOSINE TRIPHOSPHATE; MITOCHONDRIAL DNA; THYMIDINE TRIPHOSPHATE; 2'-DEOXYCYTIDINE 5'-TRIPHOSPHATE; DEOXYCYTIDINE PHOSPHATE; PYRIMIDINE NUCLEOTIDE; THYMIDINE 5'-TRIPHOSPHATE;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; DNA SYNTHESIS; EXPERIMENTAL MODEL; HUMAN; HUMAN CELL; LIVER MITOCHONDRION; MALE; METABOLIC REGULATION; MITOCHONDRIAL DNA DEPLETION; MITOCHONDRIAL DNA REPLICATION; MNGIE SYNDROME; MOLECULAR DYNAMICS; MOUSE; NONHUMAN; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; ANIMAL; CULTURE TECHNIQUE; CYTOLOGY; DNA REPLICATION; FIBROBLAST; GENETICS; METABOLISM; MITOCHONDRIAL ENCEPHALOMYOPATHY;

MURINAE;

ANIMALS; CELL CULTURE TECHNIQUES; DEOXYCYTOSINE NUCLEOTIDES; DNA REPLICATION; DNA, MITOCHONDRIAL; FIBROBLASTS; HUMANS; MICE; MITOCHONDRIA, LIVER; MITOCHONDRIAL ENCEPHALOMYOPATHIES; THYMINE NUCLEOTIDES;

EID: 79953735865     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1002035     Document Type: Article

References (33)

1. Suomalainen A, Isohanni P, (2010) Mitochondrial DNA depletion syndromes- Many genes, common mechanisms. Neuromuscul Disord 20: 429-437.
2. Bourdon A, Minai L, Serre V, Jais JP, Sarzi E, et al. (2007) Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. Nat Genet 39: 776-780.
3. Mandel H, Szargel R, Labay V, Elpeleg O, Saada A, et al. (2001) The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Nat Genet 29: 337-341.
4. Nishino I, Spinazzola A, Hirano M, (1999) Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 283: 689-692.
5. Saada A, Shaag A, Mandel H, Nevo Y, Eriksson S, et al. (2001) Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat Genet 29: 342-344.
6. Pontarin G, Fijolek A, Pizzo P, Ferraro P, Rampazzo C, et al. (2008) Ribonucleotide reduction is a cytosolic process in mammalian cells independently of DNA damage. Proc Natl Acad Sci U S A 105: 17801-17806.
7. Lopez LC, Akman HO, Garcia-Cazorla A, Dorado B, Marti R, et al. (2009) Unbalanced deoxynucleotide pools cause mitochondrial DNA instability in thymidine phosphorylase-deficient mice. Hum Mol Genet 18: 714-722.
8. Rampazzo C, Miazzi C, Franzolin E, Pontarin G, Ferraro P, et al. (2010) Regulation by degradation, a cellular defense against deoxyribonucleotide pool imbalances. Mutat Res 703: 2-10.
9. Bjursell G, Reichard P, (1973) Effects of thymidine on deoxyribonucleoside triphosphate pools and deoxyribonucleic acid synthesis in Chinese hamster ovary cells. J Biol Chem 248: 3904-3909.
10. Ferraro P, Pontarin G, Crocco L, Fabris S, Reichard P, et al. (2005) Mitochondrial deoxynucleotide pools in quiescent fibroblasts: a possible model for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). J Biol Chem 280: 24472-24480.
11. Pontarin G, Ferraro P, Valentino ML, Hirano M, Reichard P, et al. (2006) Mitochondrial DNA depletion and thymidine phosphate pool dynamics in a cellular model of mitochondrial neurogastrointestinal encephalomyopathy. J Biol Chem 281: 22720-22728.
12. Song S, Wheeler LJ, Mathews CK, (2003) Deoxyribonucleotide pool imbalance stimulates deletions in HeLa cell mitochondrial DNA. J Biol Chem 278: 43893-43896.
13. Enriquez JA, Ramos J, Perez-Martos A, Lopez-Perez MJ, Montoya J, (1994) Highly efficient DNA synthesis in isolated mitochondria from rat liver. Nucleic Acids Res 22: 1861-1865.
14. Pfaff E, Klingenberg M, (1968) Adenine nucleotide translocation of mitochondria. 1. Specificity and control. Eur J Biochem 6: 66-79.
15. Duee ED, Vignais PV, (1969) Kinetics and specificity of the adenine nucleotide translocation in rat liver mitochondria. J Biol Chem 244: 3920-3931.
16. Wang L, Saada A, Eriksson S, (2003) Kinetic properties of mutant human thymidine kinase 2 suggest a mechanism for mitochondrial DNA depletion myopathy. J Biol Chem 278: 6963-6968.
17. Wang L, Eriksson S, (2000) Cloning and characterization of full-length mouse thymidine kinase 2: the N-terminal sequence directs import of the precursor protein into mitochondria. Biochem J 351 Pt 2: 469-476.
18. Ylikallio E, Page JL, Xu X, Lampinen M, Bepler G, et al. (2010) Ribonucleotide reductase is not limiting for mitochondrial DNA copy number in mice. Nucleic Acids Res 38: 8208-8218.
19. Nishigaki Y, Marti R, Copeland WC, Hirano M, (2003) Site-specific somatic mitochondrial DNA point mutations in patients with thymidine phosphorylase deficiency. J Clin Invest 111: 1913-1921.
20. Nishigaki Y, Marti R, Hirano M, (2004) ND5 is a hot-spot for multiple atypical mitochondrial DNA deletions in mitochondrial neurogastrointestinal encephalomyopathy. Hum Mol Genet 13: 91-101.
21. Bridges EG, Jiang Z, Cheng YC, (1999) Characterization of a dCTP transport activity reconstituted from human mitochondria. J Biol Chem 274: 4620-4625.
22. Bulst S, Abicht A, Holinski-Feder E, Muller-Ziermann S, Koehler U, et al. (2009) In vitro supplementation with dAMP/dGMP leads to partial restoration of mtDNA levels in mitochondrial depletion syndromes. Hum Mol Genet 18: 1590-1599.
23. Taanman JW, Muddle JR, Muntau AC, (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.
24. Hirano M, Marti R, Casali C, Tadesse S, Uldrick T, et al. (2006) Allogeneic stem cell transplantation corrects biochemical derangements in MNGIE. Neurology 67: 1458-1460.
25. Beumer JH, Eiseman JL, Gilbert JA, Holleran JL, Yellow-Duke AE, et al. (2011) Plasma pharmacokinetics and oral bioavailability of the 3,4,5,6-tetrahydrouridine (THU) prodrug, triacetyl-THU (taTHU), in mice. Cancer Chemother Pharmacol 67: 421-430.
26. Fernandez-Vizarra E, Lopez-Perez MJ, Enriquez JA, (2002) Isolation of biogenetically competent mitochondria from mammalian tissues and cultured cells. Methods 26: 292-297.
27. Reyes A, Yasukawa T, Holt IJ, (2007) Analysis of replicating mitochondrial DNA by two-dimensional agarose gel electrophoresis. Methods Mol Biol 372: 219-232.
28. Ferraro P, Franzolin E, Pontarin G, Reichard P, Bianchi V, (2010) Quantitation of cellular deoxynucleoside triphosphates. Nucleic Acids Res 38: e85.
29. Crespo M, Sauleda S, Esteban JI, Juarez A, Ribera E, et al. (2007) Peginterferon alpha-2b plus ribavirin vs interferon alpha-2b plus ribavirin for chronic hepatitis C in HIV-coinfected patients. J Viral Hepat 14: 228-238.
30. Lai Y, Tse CM, Unadkat JD, (2004) Mitochondrial expression of the human equilibrative nucleoside transporter 1 (hENT1) results in enhanced mitochondrial toxicity of antiviral drugs. J Biol Chem 279: 4490-4497.
31. Lee EW, Lai Y, Zhang H, Unadkat JD, (2006) Identification of the mitochondrial targeting signal of the human equilibrative nucleoside transporter 1 (hENT1): implications for interspecies differences in mitochondrial toxicity of fialuridine. J Biol Chem 281: 16700-16706.
32. Ferraro P, Nicolosi L, Bernardi P, Reichard P, Bianchi V, (2006) Mitochondrial deoxynucleotide pool sizes in mouse liver and evidence for a transport mechanism for thymidine monophosphate. Proc Natl Acad Sci U S A 103: 18586-18591.
33. Antes A, Tappin I, Chung S, Lim R, Lu B, et al. (2010) Differential regulation of full-length genome and a single-stranded 7S DNA along the cell cycle in human mitochondria. Nucleic Acids Res 38: 6466-6476.