Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency

EMBO Molecular Medicine

Volumn 6, Issue 8, 2014, Pages 1016-1027

  Garone, Caterina ^a,b   Garcia Diaz, Beatriz ^a   Emmanuele, Valentina ^a,c   Lopez, Luis C ^d   Tadesse, Saba ^a   Akman, Hasan O ^a   Tanji, Kurenai ^a   Quinzii, Catarina M ^a   Hirano, Michio ^a  

^a NewYork Presbyterian Hospital   (United States)

^b UNIVERSITY OF BOLOGNA   (Italy)

^c UNIVERSITY OF GENOA   (Italy)

^d UNIVERSITY OF GRANADA   (Spain)

Author keywords

Deoxycytidine monophosphate; Deoxythymidine monophosphate; Encephalomyopathy; Therapy; Thymidine kinase

Indexed keywords

DEOXYCYTIDINE PHOSPHATE; MITOCHONDRIAL DNA; THYMIDINE KINASE; THYMIDINE KINASE 2; THYMIDINE PHOSPHATE; THYMIDINE TRIPHOSPHATE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; BIOCHEMISTRY; BRAIN CORTEX; BRAIN MITOCHONDRION; BRAIN STEM; CEREBELLUM; CONTROLLED STUDY; DRUG EFFICACY; DRUG SAFETY; ENZYME DEFICIENCY; GENETIC DISORDER; HIPPOCAMPUS; LIFESPAN; LIVER MITOCHONDRION; MITOCHONDRIAL RESPIRATION; MOLECULAR BYPASS THERAPY; MOLECULAR THERAPY; MOUSE; MOUSE MODEL; MOUSE MUTANT; NONHUMAN; PERINATAL PERIOD; PHENOTYPE; PRIORITY JOURNAL; RESPIRATORY CHAIN; REVIEW; SPINAL CORD; THYMIDINE KINASE 2 DEFICIENCY; WILD TYPE; ANIMAL; DEFICIENCY; GENE TARGETING; MITOCHONDRIAL DISEASES; SURVIVAL; TREATMENT OUTCOME;

ANIMALS; DEOXYCYTIDINE MONOPHOSPHATE; GENE KNOCK-IN TECHNIQUES; MICE; MITOCHONDRIAL DISEASES; SURVIVAL ANALYSIS; THYMIDINE KINASE; THYMIDINE MONOPHOSPHATE; TREATMENT OUTCOME;

EID: 84905408823     PISSN: 17574676     EISSN: 17574684     Source Type: Journal    
DOI: 10.15252/emmm.201404092     Document Type: Review

References (34)

1. Akman HO, Dorado B, Lopez LC, Garcia-Cazorla A, Vila MR, Tanabe LM, Dauer WT, Bonilla E, Tanji K, Hirano M (2008) Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenance. Hum Mol Genet 17: 2433-2440
2. Bourdon A, Minai L, Serre V, Jais JP, 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 mitochondrial DNA depletion. Nat Genet 39: 776-780
3. Brown NS, Bicknell R (1998) Thymidine phosphorylase, 2-deoxy-D-ribose and angiogenesis. Biochem J 334: 1-8
4. Bulst S, Abicht A, Holinski-Feder E, Muller-Ziermann S, Koehler U, Thirion C, Walter MC, Stewart JD, Chinnery PF, Lochmuller H 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
5. Copeland WC (2012) Defects in mitochondrial DNA replication and human disease. Crit Rev Biochem Mol Biol 47: 64-74
6. DiMauro S, Servidei S, Zeviani M, DiRocco M, DeVivo DC, DiDonato S, Uziel G, Berry K, Hoganson G, Johnsen SD et al (1987) Cytochrome c oxidase deficiency in Leigh syndrome. Ann Neurol 22: 498-506
7. Dorado B, Area E, Akman HO, Hirano M (2011) Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensation. Hum Mol Genet 20: 155-164
8. Elpeleg O, Miller C, Hershkovitz E, Bitner-Glindzicz M, Bondi-Rubinstein G, Rahman S, Pagnamenta A, Eshhar S, 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
9. 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 USA 103: 18586-18591
10. Ferraro P, Franzolin E, Pontarin G, Reichard P, Bianchi V (2010) Quantitation of cellular deoxynucleoside triphosphates. Nucleic Acids Res 38: e85
11. Franzolin E, Miazzi C, Frangini M, Palumbo E, Rampazzo C, Bianchi V (2012) The pyrimidine nucleotide carrier PNC1 and mitochondrial trafficking of thymidine phosphates in cultured human cells. Exp Cell Res 318: 2226-2236
12. Galbiati S, Bordoni A, Papadimitriou D, Toscano A, Rodolico C, Katsarou E, Sciacco M, Garufi A, Prelle A, Aguennouz M et al (2006) New mutations in TK2 gene associated with mitochondrial DNA depletion. Pediatr Neurol 34: 177-185
13. Garone C, Tadesse S, Hirano M (2011) Clinical and genetic spectrum of mitochondrial neurogastrointestinal encephalomyopathy. Brain 134: 3326-3332
14. Gotz A, Isohanni P, Pihko H, Paetau A, Herva R, Saarenpaa-Heikkila O, Valanne L, Marjavaara S, Suomalainen A (2008) Thymidine kinase 2 defects can cause multi-tissue mtDNA depletion syndrome. Brain 131: 2841-2850
15. Heinemann V, Plunkett W (1989) Modulation of deoxynucleotide metabolism by the deoxycytidylate deaminase inhibitor 3, 4, 5, 6-tetrahydrodeoxyuridine. Bioch Pharmacol 38: 4115-4121
16. Hirano M, Marti R, Ferreiro-Barros C, Vilà MR, Tadesse S, Nishigaki Y, Nishino I, Vu TH (2001) Defects of intergenomic communication: autosomal disorders that cause multiple deletions and depletion of mitochondrial DNA. Semin Cell Biol Develop 12: 417-427
17. Hirano M, Nishigaki Y, Martí R (2004) MNGIE: a disease of two genomes. Neurologist 10: 8-17
18. Hirano M, Marti R, Casali C, Tadesse S, Uldrick T, Fine B, Escolar DM, Valentino ML, Nishino I, Hesdorffer C et al (2006) Allogeneic stem cell transplantation corrects biochemical derangements in MNGIE. Neurology 67: 1458-1460
19. Jansen RS, Rosing H, Schellens JH, Beijnen JH (2011) Deoxyuridine analog nucleotides in deoxycytidine analog treatment: secondary active metabolites? Fundam Clin Pharmacol 25: 172-185
20. Lopez LC, Akman HO, Garcia-Cazorla A, Dorado B, Marti R, Nishino I, Tadesse S, Pizzorno G, Shungu D, Bonilla E et al (2009) Unbalanced deoxynucleotide pools cause mitochondrial DNA instability in thymidine phosphorylase deficient mice. Hum Mol Genet 18: 714-722
21. 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 kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Nat Genet 29: 337-341
22. Marti R, Dorado B, Hirano M (2012a) Measurement of mitochondrial dNTP pools. Methods Mol Biol 837: 135-148
23. Marti R, Lopez LC, Hirano M (2012b) Assessment of thymidine phosphorylase function: measurement of plasma thymidine (and deoxyuridine) and thymidine phosphorylase activity. Methods Mol Biol 837: 121-133
24. Martí R, Nishigaki Y, Hirano M (2003) Elevated plasma deoxyuridine in patients with thymidine phosphorylase deficiency. Biochem Biophys Res Commun 303: 14-18
25. Naviaux RK, Nguyen KV (2004) POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. Ann Neurol 55: 706-712
26. Nishino I, Spinazzola A, Hirano M (1999) Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 283: 689-692
27. Ostergaard E, Christensen E, Kristensen E, Mogensen B, Duno M, Shoubridge EA, 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
28. Saada A, Shaag A, Mandel H, Nevo Y, Eriksson S, Elpeleg O (2001) Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat Genet 29: 342-344
29. Saada A, Ben-Shalom E, Zyslin R, Miller C, Mandel H, Elpeleg O (2003) Mitochondrial deoxyribonucleoside triphosphate pools in thymidine kinase 2 deficiency. Biochem Biophys Res Commun 310: 963-966
30. Sarzi E, Goffart S, Serre V, Chretien D, Slama A, Munnich A, Spelbrink JN, Rotig A (2007) Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA depletion. Ann Neurol 62: 579-587
31. Spinazzola A, Viscomi C, Fernandez-Vizarra E, Carrara F, D'Adamo P, Calvo S, Marsano RM, 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
32. Spinazzola A, Zeviani M (2009) Mitochondrial diseases: a cross-talk between mitochondrial and nuclear genomes. Adv Exp Med Biol 652: 69-84
33. Tyynismaa H, Sun R, Ahola-Erkkila S, Almusa H, Poyhonen R, Korpela M, Honkaniemi J, Isohanni P, Paetau A, Wang L et al (2012) Thymidine kinase 2 mutations in autosomal recessive progressive external ophthalmoplegia with multiple mitochondrial DNA deletions. Hum Mol Genet 21: 66-75
34. Zhou X, Solaroli N, Bjerke M, Stewart JB, Rozell B, Johansson M, Karlsson A (2008) Progressive loss of mitochondrial DNA in thymidine kinase 2-deficient mice. Hum Mol Genet 17: 2329-2335