Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 29 January 1999:
Vol. 283. no. 5402, pp. 689 - 692
DOI: 10.1126/science.283.5402.689
Prev | Table of Contents | Next

Reports

Thymidine Phosphorylase Gene Mutations in MNGIE, a Human Mitochondrial Disorder

Ichizo Nishino, Antonella Spinazzola, Michio Hirano *

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive human disease associated with multiple deletions of skeletal muscle mitochondrial DNA (mtDNA), which have been ascribed to a defect in communication between the nuclear and mitochondrial genomes. Examination of 12 MNGIE probands revealed homozygous or compound-heterozygous mutations in the gene specifying thymidine phosphorylase (TP), located on chromosome 22q13.32-qter. TP activity in leukocytes from MNGIE patients was less than 5 percent of controls, indicating that loss-of-function mutations in TP cause the disease. The pathogenic mechanism may be related to aberrant thymidine metabolism, leading to impaired replication or maintenance of mtDNA, or both.

Columbia University College of Physicians and Surgeons, Department of Neurology, 630 West 168 Street, P & S 4-443, New York, NY 10032, USA.
*   To whom correspondence should be addressed. E-mail: mh29{at}columbia.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Diagnosis and therapy in neuromuscular disorders: diagnosis and new treatments in mitochondrial diseases.
S Rahman and M G Hanna (2009)
J. Neurol. Neurosurg. Psychiatry 80, 943-953
   Abstract »    Full Text »    PDF »
Antiangiogenic and Antitumor Activity of 6-(2-Aminoethyl)Amino-5-Chlorouracil, a Novel Small-Molecule Inhibitor of Thymidine Phosphorylase, in Combination with the Vascular Endothelial Growth Factor-Trap.
H. Lu, R. S. Klein, and E. L. Schwartz (2009)
Clin. Cancer Res. 15, 5136-5144
   Abstract »    Full Text »    PDF »
Mitochondrial Neurogastrointestinal Encephalopathy Due to Mutations in RRM2B.
A. Shaibani, O. A. Shchelochkov, S. Zhang, P. Katsonis, O. Lichtarge, L.-J. Wong, and M. Shinawi (2009)
Arch Neurol 66, 1028-1032
   Abstract »    Full Text »    PDF »
The pathophysiology of mitochondrial disease as modeled in the mouse.
D. C. Wallace and W. Fan (2009)
Genes & Dev. 23, 1714-1736
   Abstract »    Full Text »    PDF »
In vitro supplementation with dAMP/dGMP leads to partial restoration of mtDNA levels in mitochondrial depletion syndromes.
S. Bulst, A. Abicht, E. Holinski-Feder, S. Muller-Ziermann, U. Koehler, C. Thirion, M. C. Walter, J. D. Stewart, P. F. Chinnery, H. Lochmuller, et al. (2009)
Hum. Mol. Genet. 18, 1590-1599
   Abstract »    Full Text »    PDF »
Gene Regulation and Functional Alterations Induced by Kaposi's Sarcoma-Associated Herpesvirus-Encoded ORFK13/vFLIP in Endothelial Cells.
S. Sakakibara, C. A. Pise-Masison, J. N. Brady, and G. Tosato (2009)
J. Virol. 83, 2140-2153
   Abstract »    Full Text »    PDF »
Unbalanced deoxynucleotide pools cause mitochondrial DNA instability in thymidine phosphorylase-deficient mice.
L. C. Lopez, H. O. Akman, A. Garcia-Cazorla, B. Dorado, R. Marti, I. Nishino, S. Tadesse, G. Pizzorno, D. Shungu, E. Bonilla, et al. (2009)
Hum. Mol. Genet. 18, 714-722
   Abstract »    Full Text »    PDF »
Early-onset liver mtDNA depletion and late-onset proteinuric nephropathy in Mpv17 knockout mice.
C. Viscomi, A. Spinazzola, M. Maggioni, E. Fernandez-Vizarra, V. Massa, C. Pagano, R. Vettor, M. Mora, and M. Zeviani (2009)
Hum. Mol. Genet. 18, 12-26
   Abstract »    Full Text »    PDF »
Diagnosis of mitochondrial DNA depletion syndromes.
S. Rahman and J. Poulton (2009)
Arch. Dis. Child. 94, 3-5
   Full Text »    PDF »
CARRIER ERYTHROCYTE ENTRAPPED THYMIDINE PHOSPHORYLASE THERAPY FOR MNGIE.
N. F. Moran, M. D. Bain, M.M.K. Muqit, and B. E. Bax (2008)
Neurology 71, 686-688
   Full Text »    PDF »
Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenance.
H. O. Akman, B. Dorado, L. C. Lopez, A. Garcia-Cazorla, M. R. Vila, L. M. Tanabe, W. T. Dauer, E. Bonilla, K. Tanji, and M. Hirano (2008)
Hum. Mol. Genet. 17, 2433-2440
   Abstract »    Full Text »    PDF »
Depletion of mitochondrial DNA in fibroblast cultures from patients with POLG1 mutations is a consequence of catalytic mutations.
N. Ashley, A. O'Rourke, C. Smith, S. Adams, V. Gowda, M. Zeviani, G. K. Brown, C. Fratter, and J. Poulton (2008)
Hum. Mol. Genet. 17, 2496-2506
   Abstract »    Full Text »    PDF »
Identification of a putative human mitochondrial thymidine monophosphate kinase associated with monocytic/macrophage terminal differentiation..
Y.-L. Chen, D.-W. Lin, and Z.-F. Chang (2008)
Genes Cells 13, 679-689
   Abstract »    Full Text »    PDF »
Metabolic Interrelations within Guanine Deoxynucleotide Pools for Mitochondrial and Nuclear DNA Maintenance.
L. Leanza, P. Ferraro, P. Reichard, and V. Bianchi (2008)
J. Biol. Chem. 283, 16437-16445
   Abstract »    Full Text »    PDF »
Kinetic Investigation of the Inhibitory Effect of Gemcitabine on DNA Polymerization Catalyzed by Human Mitochondrial DNA Polymerase.
J. D. Fowler, J. A. Brown, K. A. Johnson, and Z. Suo (2008)
J. Biol. Chem. 283, 15339-15348
   Abstract »    Full Text »    PDF »
OPA1 mutations and mitochondrial DNA damage: keeping the magic circle in shape.
M. Zeviani (2008)
Brain 131, 314-317
   Full Text »    PDF »
Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance.
G. Hudson, P. Amati-Bonneau, E. L. Blakely, J. D. Stewart, L. He, A. M. Schaefer, P. G. Griffiths, K. Ahlqvist, A. Suomalainen, P. Reynier, et al. (2008)
Brain 131, 329-337
   Abstract »    Full Text »    PDF »
OPA1 mutations induce mitochondrial DNA instability and optic atrophy 'plus' phenotypes.
P. Amati-Bonneau, M. L. Valentino, P. Reynier, M. E. Gallardo, B. Bornstein, A. Boissiere, Y. Campos, H. Rivera, J. G. de la Aleja, R. Carroccia, et al. (2008)
Brain 131, 338-351
   Abstract »    Full Text »    PDF »
Human UMP-CMP Kinase 2, a Novel Nucleoside Monophosphate Kinase Localized in Mitochondria.
Y. Xu, M. Johansson, and A. Karlsson (2008)
J. Biol. Chem. 283, 1563-1571
   Abstract »    Full Text »    PDF »
Mitochondrial Thymidine Kinase and the Enzymatic Network Regulating Thymidine Triphosphate Pools in Cultured Human Cells.
C. Rampazzo, S. Fabris, E. Franzolin, K. Crovatto, M. Frangini, and V. Bianchi (2007)
J. Biol. Chem. 282, 34758-34769
   Abstract »    Full Text »    PDF »
Maintaining precursor pools for mitochondrial DNA replication.
C. K. Mathews and S. Song (2007)
FASEB J 21, 2294-2303
   Abstract »    Full Text »    PDF »
Defects in maintenance of mitochondrial DNA are associated with intramitochondrial nucleotide imbalances.
N. Ashley, S. Adams, A. Slama, M. Zeviani, A. Suomalainen, A. L. Andreu, R. K. Naviaux, and J. Poulton (2007)
Hum. Mol. Genet. 16, 1400-1411
   Abstract »    Full Text »    PDF »
Mutations in SUCLA2: a tandem ride back to the Krebs cycle.
P. F. Chinnery (2007)
Brain 130, 606-609
   Full Text »    PDF »
Treatment of Mitochondrial Neurogastrointestinal Encephalomyopathy With Dialysis.
H. Yavuz, A. Ozel, M. Christensen, E. Christensen, M. Schwartz, M. Elmaci, and J. Vissing (2007)
Arch Neurol 64, 435-438
   Abstract »    Full Text »    PDF »
Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations.
E. Ostergaard, F. J. Hansen, N. Sorensen, M. Duno, J. Vissing, P. L. Larsen, O. Faeroe, S. Thorgrimsson, F. Wibrand, E. Christensen, et al. (2007)
Brain 130, 853-861
   Abstract »    Full Text »    PDF »
Mitochondrial deoxynucleotide pool sizes in mouse liver and evidence for a transport mechanism for thymidine monophosphate.
P. Ferraro, L. Nicolosi, P. Bernardi, P. Reichard, and V. Bianchi (2006)
PNAS 103, 18586-18591
   Abstract »    Full Text »    PDF »
Treating MNGIE: Is reducing blood nucleosides the first cure for a mitochondrial disorder?.
P. F. Chinnery and J. Vissing (2006)
Neurology 67, 1330-1332
   Full Text »    PDF »
Infusion of platelets transiently reduces nucleoside overload in MNGIE.
M. C. Lara, B. Weiss, I. Illa, P. Madoz, L. Massuet, A. L. Andreu, M. L. Valentino, Y. Anikster, M. Hirano, and R. Marti (2006)
Neurology 67, 1461-1463
   Abstract »    Full Text »    PDF »
Allogeneic stem cell transplantation corrects biochemical derangements in MNGIE.
M. Hirano, R. Marti, C. Casali, S. Tadesse, T. Uldrick, B. Fine, D. M. Escolar, M. L. Valentino, I. Nishino, C. Hesdorffer, et al. (2006)
Neurology 67, 1458-1460
   Abstract »    Full Text »    PDF »
Mitochondrial DNA polymerase-{gamma} and human disease.
G. Hudson and P. F. Chinnery (2006)
Hum. Mol. Genet. 15, R244-R252
   Abstract »    Full Text »    PDF »
Mitochondrial DNA Depletion and Thymidine Phosphate Pool Dynamics in a Cellular Model of Mitochondrial Neurogastrointestinal Encephalomyopathy.
G. Pontarin, P. Ferraro, M. L. Valentino, M. Hirano, P. Reichard, and V. Bianchi (2006)
J. Biol. Chem. 281, 22720-22728
   Abstract »    Full Text »    PDF »
Hepatocerebral Mitochondrial DNA Depletion Syndrome Caused by Deoxyguanosine Kinase (DGUOK) Mutations..
P. Freisinger, N. Futterer, E. Lankes, K. Gempel, T. M. Berger, J. Spalinger, A. Hoerbe, C. Schwantes, M. Lindner, R. Santer, et al. (2006)
Arch Neurol 63, 1129-1134
   Abstract »    Full Text »    PDF »
A polymorphic polymerase..
S. DiMauro, G. Davidzon, and M. Hirano (2006)
Brain 129, 1637-1639
   Full Text »    PDF »
DNA precursor metabolism and genomic stability.
C. K. Mathews (2006)
FASEB J 20, 1300-1314
   Abstract »    Full Text »    PDF »
Diagnosis and Management of Adult Patients With Chronic Intestinal Pseudoobstruction.
D. H. Sutton, S. P. Harrell, and J. M. Wo (2006)
Nutr Clin Pract 21, 16-22
   Abstract »    Full Text »    PDF »
Mitochondrial abnormalities in inclusion-body myositis.
A. Oldfors, A. R. Moslemi, L. Jonasson, M. Ohlsson, G. Kollberg, and C. Lindberg (2006)
Neurology 66, S49-S55
   Abstract »    Full Text »    PDF »
Simultaneous Detection and Quantification of Mitochondrial DNA Deletion(s), Depletion, and Over-Replication in Patients with Mitochondrial Disease.
R.-K. Bai and L.-J. C. Wong (2005)
J. Mol. Diagn. 7, 613-622
   Abstract »    Full Text »    PDF »
Mitochondrial DNA copy number threshold in mtDNA depletion myopathy.
S. E. Durham, E. Bonilla, D. C. Samuels, S. DiMauro, and P. F. Chinnery (2005)
Neurology 65, 453-455
   Abstract »    Full Text »    PDF »
Predominant Cerebellar Volume Loss as a Neuroradiologic Feature of Pediatric Respiratory Chain Defects.
F. Scaglia, L.-J. C. Wong, G. D. Vladutiu, and J. V. Hunter (2005)
AJNR Am. J. Neuroradiol. 26, 1675-1680
   Abstract »    Full Text »    PDF »
Mitochondrial Deoxynucleotide Pools in Quiescent Fibroblasts: A POSSIBLE MODEL FOR MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOMYOPATHY (MNGIE).
P. Ferraro, G. Pontarin, L. Crocco, S. Fabris, P. Reichard, and V. Bianchi (2005)
J. Biol. Chem. 280, 24472-24480
   Abstract »    Full Text »    PDF »
The Conserved Mec1/Rad53 Nuclear Checkpoint Pathway Regulates Mitochondrial DNA Copy Number in Saccharomyces cerevisiae.
S. D. Taylor, H. Zhang, J. S. Eaton, M. S. Rodeheffer, M. A. Lebedeva, T. W. O'Rourke, W. Siede, and G. S. Shadel (2005)
Mol. Biol. Cell 16, 3010-3018
   Abstract »    Full Text »    PDF »
DNA precursor asymmetries in mammalian tissue mitochondria and possible contribution to mutagenesis through reduced replication fidelity.
S. Song, Z. F. Pursell, W. C. Copeland, M. J. Longley, T. A. Kunkel, and C. K. Mathews (2005)
PNAS 102, 4990-4995
   Abstract »    Full Text »    PDF »
Mutations in the Spacer Region of Drosophila Mitochondrial DNA Polymerase Affect DNA Binding, Processivity, and the Balance between Pol and Exo Function.
N. Luo and L. S. Kaguni (2005)
J. Biol. Chem. 280, 2491-2497
   Abstract »    Full Text »    PDF »
Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number.
H. Tyynismaa, H. Sembongi, M. Bokori-Brown, C. Granycome, N. Ashley, J. Poulton, A. Jalanko, J. N. Spelbrink, I. J. Holt, and A. Suomalainen (2004)
Hum. Mol. Genet. 13, 3219-3227
   Abstract »    Full Text »    PDF »
Lack of gastrointestinal symptoms in a 60-year-old patient with MNGIE.
M. A. Martin, A. Blazquez, R. Marti, J. Bautista, M. C. Lara, A. Cabello, Y. Campos, O. Belda, A. L. Andreu, and J. Arenas (2004)
Neurology 63, 1536-1537
   Full Text »    PDF »
POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement.
G. Van Goethem, P. Luoma, M. Rantamaki, A. Al Memar, S. Kaakkola, P. Hackman, R. Krahe, A. Lofgren, J. J. Martin, P. De Jonghe, et al. (2004)
Neurology 63, 1251-1257
   Abstract »    Full Text »    PDF »
Mitochondrial disorders.
M. Zeviani and S. Di Donato (2004)
Brain 127, 2153-2172
   Abstract »    Full Text »    PDF »
Functional and genetic studies demonstrate that mutation in the COX15 gene can cause Leigh syndrome.
C E Oquendo, H Antonicka, E A Shoubridge, W Reardon, and G K Brown (2004)
J. Med. Genet. 41, 540-544
   Full Text »    PDF »
Twinkle and POLG defects enhance age-dependent accumulation of mutations in the control region of mtDNA.
S. Wanrooij, P. Luoma, G. van Goethem, C. van Broeckhoven, A. Suomalainen, and J. N. Spelbrink (2004)
Nucleic Acids Res. 32, 3053-3064
   Abstract »    Full Text »    PDF »
Mitochondrial Deoxyribonucleotides, Pool Sizes, Synthesis, and Regulation.
C. Rampazzo, P. Ferraro, G. Pontarin, S. Fabris, P. Reichard, and V. Bianchi (2004)
J. Biol. Chem. 279, 17019-17026
   Abstract »    Full Text »    PDF »
Crystal Structures of the Mitochondrial Deoxyribonucleotidase in Complex with Two Specific Inhibitors.
A. Rinaldo-Matthis, C. Rampazzo, J. Balzarini, P. Reichard, V. Bianchi, and P. Nordlund (2004)
Mol. Pharmacol. 65, 860-867
   Abstract »    Full Text »
Inhibition of Metastasis of Tumor Cells Overexpressing Thymidine Phosphorylase by 2-Deoxy-L-Ribose.
Y. Nakajima, T. Gotanda, H. Uchimiya, T. Furukawa, M. Haraguchi, R. Ikeda, T. Sumizawa, H. Yoshida, and S.-i. Akiyama (2004)
Cancer Res. 64, 1794-1801
   Abstract »    Full Text »    PDF »
MNGIE with lack of skeletal muscle involvement and a novel TP splice site mutation.
K Szigeti, L-J C Wong, C-L Perng, G M Saifi, K Eldin, A M Adesina, D L Cass, M Hirano, J R Lupski, and F Scaglia (2004)
J. Med. Genet. 41, 125-129
   Abstract »    Full Text »    PDF »
ND5 is a hot-spot for multiple atypical mitochondrial DNA deletions in mitochondrial neurogastrointestinal encephalomyopathy.
Y. Nishigaki, R. Marti, and M. Hirano (2004)
Hum. Mol. Genet. 13, 91-101
   Abstract »    Full Text »    PDF »
The Podospora rmp1 Gene Implicated in Nucleus-Mitochondria Cross-Talk Encodes an Essential Protein Whose Subcellular Location Is Developmentally Regulated.
V. Contamine, D. Zickler, and M. Picard (2004)
Genetics 166, 135-150
   Abstract »    Full Text »    PDF »
Definitive Diagnosis of Mitochondrial Neurogastrointestinal Encephalomyopathy by Biochemical Assays.
R. Marti, A. Spinazzola, S. Tadesse, I. Nishino, Y. Nishigaki, and M. Hirano (2004)
Clin. Chem. 50, 120-124
   Abstract »    Full Text »    PDF »
Genetic Features of Mitochondrial Respiratory Chain Disorders.
A. Rotig and A. Munnich (2003)
J. Am. Soc. Nephrol. 14, 2995-3007
   Abstract »    Full Text »    PDF »
Deoxyribonucleotide Pool Imbalance Stimulates Deletions in HeLa Cell Mitochondrial DNA.
S. Song, L. J. Wheeler, and C. K. Mathews (2003)
J. Biol. Chem. 278, 43893-43896
   Abstract »    Full Text »    PDF »
Techniques and Pitfalls in the Detection of Pathogenic Mitochondrial DNA Mutations.
C. T. Moraes, D. P. Atencio, J. Oca-Cossio, and F. Diaz (2003)
J. Mol. Diagn. 5, 197-208
   Abstract »    Full Text »    PDF »
Mitochondrial disorders come full circle.
P. F. Chinnery (2003)
Neurology 61, 878-880
   Full Text »    PDF »
Remarkable infidelity of polymerase {gamma}A associated with mutations in POLG1 exonuclease domain.
R. Del Bo, A. Bordoni, M. Sciacco, A. Di Fonzo, S. Galbiati, M. Crimi, N. Bresolin, and G. P. Comi (2003)
Neurology 61, 903-908
   Abstract »    Full Text »    PDF »
Origins of mitochondrial thymidine triphosphate: Dynamic relations to cytosolic pools.
G. Pontarin, L. Gallinaro, P. Ferraro, P. Reichard, and V. Bianchi (2003)
PNAS 100, 12159-12164
   Abstract »    Full Text »    PDF »
Mitochondria.
P F Chinnery and E A Schon (2003)
J. Neurol. Neurosurg. Psychiatry 74, 1188-1199
   Abstract »    Full Text »    PDF »
Clinical and Genetic Heterogeneity in Progressive External Ophthalmoplegia Due to Mutations in Polymerase {gamma}.
M. Filosto, M. Mancuso, Y. Nishigaki, J. Pancrudo, Y. Harati, C. Gooch, A. Mankodi, L. Bayne, E. Bonilla, S. Shanske, et al. (2003)
Arch Neurol 60, 1279-1284
   Abstract »    Full Text »    PDF »
POS5 Gene of Saccharomyces cerevisiae Encodes a Mitochondrial NADH Kinase Required for Stability of Mitochondrial DNA.
M. K. Strand, G. R. Stuart, M. J. Longley, M. A. Graziewicz, O. C. Dominick, and W. C. Copeland (2003)
Eukaryot. Cell 2, 809-820
   Abstract »    Full Text »    PDF »
Mitochondrial Respiratory-Chain Diseases.
S. DiMauro and E. A. Schon (2003)
N. Engl. J. Med. 348, 2656-2668
   Full Text »    PDF »
Substoichiometric shifting in the plant mitochondrial genome is influenced by a gene homologous to MutS.
R. V. Abdelnoor, R. Yule, A. Elo, A. C. Christensen, G. Meyer-Gauen, and S. A. Mackenzie (2003)
PNAS 100, 5968-5973
   Abstract »    Full Text »    PDF »
Role of MHC Class I in Immune Surveillance of Mitochondrial DNA Integrity.
Y. Gu, C. Wang, C. M. Roifman, and A. Cohen (2003)
J. Immunol. 170, 3603-3607
   Abstract »    Full Text »    PDF »
Defective mitochondrial DNA replication and NRTIs: pathophysiological implications in AIDS cardiomyopathy.
W. Lewis (2003)
Am J Physiol Heart Circ Physiol 284, H1-H9
   Full Text »    PDF »
Mitochondrial DNA depletion: Mutations in thymidine kinase gene with myopathy and SMA.
M. Mancuso, L. Salviati, S. Sacconi, D. Otaegui, P. Camano, A. Marina, S. Bacman, C.T. Moraes, J.R. Carlo, M. Garcia, et al. (2002)
Neurology 59, 1197-1202
   Abstract »    Full Text »    PDF »
Multiple mtDNA deletions with features of MNGIE.
J. Vissing, K. Ravn, E.R. Danielsen, M. Duno, F. Wibrand, R.A. Wevers, and M. Schwartz (2002)
Neurology 59, 926-929
   Abstract »    Full Text »    PDF »
Human Mitochondrial 5'-Deoxyribonucleotidase. OVERPRODUCTION IN CULTURED CELLS AND FUNCTIONAL ASPECTS.
L. Gallinaro, K. Crovatto, C. Rampazzo, G. Pontarin, P. Ferraro, E. Milanesi, P. Reichard, and V. Bianchi (2002)
J. Biol. Chem. 277, 35080-35087
   Abstract »    Full Text »    PDF »
Phenotypic variability in a Spanish family with MNGIE.
J. Gamez, C. Ferreiro, M. L. Accarino, L. Guarner, S. Tadesse, R. A. Marti, A. L. Andreu, N. Raguer, C. Cervera, and M. Hirano (2002)
Neurology 59, 455-457
   Abstract »    Full Text »    PDF »
Two Copies of mthmg1, Encoding a Novel Mitochondrial HMG-Like Protein, Delay Accumulation of Mitochondrial DNA Deletions in Podospora anserina.
M. Dequard-Chablat and C. Alland (2002)
Eukaryot. Cell 1, 503-513
   Abstract »    Full Text »    PDF »
Targeted Deletion of Both Thymidine Phosphorylase and Uridine Phosphorylase and Consequent Disorders in Mice.
M. Haraguchi, H. Tsujimoto, M. Fukushima, I. Higuchi, H. Kuribayashi, H. Utsumi, A. Nakayama, Y. Hashizume, J. Hirato, H. Yoshida, et al. (2002)
Mol. Cell. Biol. 22, 5212-5221
   Abstract »    Full Text »    PDF »
Active Site Mutation in DNA Polymerase gamma Associated with Progressive External Ophthalmoplegia Causes Error-prone DNA Synthesis.
M. V. Ponamarev, M. J. Longley, D. Nguyen, T. A. Kunkel, and W. C. Copeland (2002)
J. Biol. Chem. 277, 15225-15228
   Abstract »    Full Text »    PDF »
Release of replication termination controls mitochondrial DNA copy number after depletion with 2',3'-dideoxycytidine.
T. A. Brown and D. A. Clayton (2002)
Nucleic Acids Res. 30, 2004-2010
   Abstract »    Full Text »    PDF »
Suppression of Thymidine Phosphorylase-mediated Angiogenesis and Tumor Growth by 2-Deoxy-L-ribose.
H. Uchimiya, T. Furukawa, M. Okamoto, Y. Nakajima, S. Matsushita, R. Ikeda, T. Gotanda, M. Haraguchi, T. Sumizawa, M. Ono, et al. (2002)
Cancer Res. 62, 2834-2839
   Abstract »    Full Text »    PDF »
Mitochondrial DNA Somatic Mutations (Point Mutations and Large Deletions) and Mitochondrial DNA Variants in Human Thyroid Pathology : A Study with Emphasis on Hurthle Cell Tumors.
V. Maximo, P. Soares, J. Lima, J. Cameselle-Teijeiro, and M. Sobrinho-Simoes (2002)
Am. J. Pathol. 160, 1857-1865
   Abstract »    Full Text »    PDF »
The "new" mitochondrial disorders.
A H V Schapira (2002)
J. Neurol. Neurosurg. Psychiatry 72, 144-149
   Abstract »    Full Text »    PDF »
Altered Thymidine Metabolism Due to Defects of Thymidine Phosphorylase.
A. Spinazzola, R. Marti, I. Nishino, A. L. Andreu, A. Naini, S. Tadesse, I. Pela, E. Zammarchi, M. A. Donati, J. A. Oliver, et al. (2002)
J. Biol. Chem. 277, 4128-4133
   Abstract »    Full Text »    PDF »
ANT1,Twinkle,POLG, and TP: New genes open our eyes to ophthalmoplegia.
M. Hirano and S. DiMauro (2001)
Neurology 57, 2163-2165
   Full Text »    PDF »
Nuclear genetic defects of oxidative phosphorylation.
E. A. Shoubridge (2001)
Hum. Mol. Genet. 10, 2277-2284
   Abstract »    Full Text »    PDF »
Mitochondrial DNA transfer RNA gene sequence variations in patients with mitochondrial disorders.
D. Sternberg, E. Chatzoglou, P. Laforet, G. Fayet, C. Jardel, P. Blondy, M. Fardeau, S. Amselem, B. Eymard, and A. Lombes (2001)
Brain 124, 984-994
   Abstract »    Full Text »    PDF »
CD24 Induces Apoptosis in Human B Cells Via the Glycolipid-Enriched Membrane Domains/Rafts-Mediated Signaling System.
T. Suzuki, N. Kiyokawa, T. Taguchi, T. Sekino, Y. U. Katagiri, and J. Fujimoto (2001)
J. Immunol. 166, 5567-5577
   Abstract »    Full Text »    PDF »
Synthesis of mitochondrial DNA in permeabilised human cultured cells.
C. F. Emmerson, G. K. Brown, and J. Poulton (2001)
Nucleic Acids Res. 29, e1
   Abstract »    Full Text »    PDF »
Mitochondrial enteropathy: the primary pathology may not be within the gastrointestinal tract.
P F Chinnery, S Jones, L Sviland, R M Andrews, T J Parsons, D M Turnbull, and L A Bindoff (2001)
Gut 48, 121-124
   Abstract »    Full Text »    PDF »
Human mtDNA sublimons resemble rearranged mitochondrial genomes found in pathological states.
O. A. Kajander, A. T. Rovio, K. Majamaa, J. Poulton, J. N. Spelbrink, I. J. Holt, P. J. Karhunen, and H. T. Jacobs (2000)
Hum. Mol. Genet. 9, 2821-2835
   Abstract »    Full Text »    PDF »
Role of Adenine Nucleotide Translocator 1 in mtDNA Maintenance.
J. Kaukonen, J. K. Juselius, V. Tiranti, A. Kyttälä, M. Zeviani, G. P. Comi, S. Keränen, L. Peltonen, and A. Suomalainen (2000)
Science 289, 782-785
   Abstract »    Full Text »
A deoxyribonucleotidase in mitochondria: Involvement in regulation of dNTP pools and possible link to genetic disease.
C. Rampazzo, L. Gallinaro, E. Milanesi, E. Frigimelica, P. Reichard, and V. Bianchi (2000)
PNAS 97, 8239-8244
   Abstract »    Full Text »    PDF »
Further evidence for genetic heterogeneity of autosomal dominant disorders with accumulation of multiple deletions of mitochondrial DNA.
G. VAN GOETHEM, A. LÖFGREN, J.-J. MARTIN, and C. VAN BROECKHOVEN (2000)
J. Med. Genet. 37, 547-548
   Full Text »
Mitochondrial Basis for Immune Deficiency: Evidence from Purine Nucleoside Phosphorylase-Deficient Mice.
E. Arpaia, P. Benveniste, A. Di Cristofano, Y. Gu, I. Dalal, S. Kelly, M. Hershfield, P. P. Pandolfi, C. M. Roifman, and A. Cohen (2000)
J. Exp. Med. 191, 2197-2208
   Abstract »    Full Text »    PDF »
Maintenance and Integrity of the Mitochondrial Genome: a Plethora of Nuclear Genes in the Budding Yeast.
V. Contamine and M. Picard (2000)
Microbiol. Mol. Biol. Rev. 64, 281-315
   Abstract »    Full Text »    PDF »
Familial Mitochondrial Intestinal Pseudo-Obstruction and Neurogenic Bladder.
L. T. Haftel, D. Lev, V. Barash, A. Gutman, Y. Bujanover, and T. Lerman-Sagie (2000)
J Child Neurol 15, 386-389
   Abstract »    PDF »
Rearrangements of Human Mitochondrial DNA (mtDNA): New Insights into the Regulation of mtDNA Copy Number and Gene Expression.
Y. Tang, E. A. Schon, E. Wilichowski, M. E. Vazquez-Memije, E. Davidson, and M. P. King (2000)
Mol. Biol. Cell 11, 1471-1485
   Abstract »    Full Text »
Does the Patient Have a Mitochondrial Encephalomyopathy?.
S. DiMauro, E. Bonilla, and D. C. De Vivo (1999)
J Child Neurol 14, S23-S35
   Abstract »    PDF »
Mapping of autosomal dominant progressive external ophthalmoplegia to a 7-cM critical region on 10q24.
F. Y. Li, M. Tariq, R. Croxen, K. Morten, W. Squier, J. Newsom-Davis, D. Beeson, and C. Larsson (1999)
Neurology 53, 1265
   Abstract »    Full Text »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)