Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

See all formats and pricing
More options …
Volume 41, Issue 7


Alteration of Nucleotide Metabolism: A New Mechanism for Mitochondrial Disorders

Ramon Martí / Yutaka Nishigaki / Maya R. Vilá / Michio Hirano
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/CCLM.2003.128


Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disease caused by loss-of-function mutations in the gene encoding thymidine phosphorylase (TP). TP deficiency alters the metabolism of the nucleosides thymidine and deoxyuridine, which, in turn, produces abnormalities of mitochondrial DNA (mtDNA) including depletion, deletions, and point mutations. MNGIE is the best characterized of the expanding number of mitochondrial disorders caused by alterations in the metabolism of nucleosides/nucleotides. Because mitochondria contain their own machinery for nucleoside and nucleotide metabolism and have physically separate nucleotide pools, it is not surprising that disorders of these pathways cause human diseases. Other diseases in this group include mtDNA depletion syndromes caused by mutations on the nuclear genes encoding the mitochondrial thymidine kinase and deoxyguanosine kinase; autosomal dominant progressive external ophthalmoplegia with multiple deletions of mtDNA due to mutations in the genes encoding the muscle-isoform of mitochondrial ADP/ATP translocator; and mitochondrial DNA depletion due to toxicities of nucleoside analogues. Mutations in the deoxynucleotide carrier, a transporter of deoxynucleoside diphosphates, have been identified as a cause of congenital microcephaly. However, alterations of mtDNA have not yet been established in this disorder. Future studies are likely to reveal additional diseases and provide further insight into this new subject.

About the article

Published Online: 2005-06-01

Published in Print: 2003-07-21

Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 41, Issue 7, Pages 845–851, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2003.128.

Export Citation

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Ivano Di Meo, Costanza Lamperti, and Valeria Tiranti
EMBO Molecular Medicine, 2015, Volume 7, Number 10, Page 1257
Russell P. Saneto, Seth D. Friedman, and Dennis W.W. Shaw
Mitochondrion, 2008, Volume 8, Number 5-6, Page 396
Javier Torres-Torronteras, Raquel Cabrera-Pérez, Ferran Vila-Julia, Carlo Viscomi, Yolanda Cámara, Michio Hirano, Massimo Zeviani, and Ramon Marti
Human Gene Therapy, 2017
Patrick C. Bradshaw and David C. Samuels
American Journal of Physiology-Cell Physiology, 2005, Volume 288, Number 5, Page C989
Rajgopal Govindarajan, Aimee H. Bakken, Kelly L. Hudkins, Yurong Lai, F. Javier Casado, Marçal Pastor-Anglada, Chung-Ming Tse, Jun Hayashi, and Jashvant D. Unadkat
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2007, Volume 293, Number 5, Page R1809
Javier Torres-Torronteras, Raquel Cabrera-Pérez, Ignasi Barba, Carme Costa, Noemí de Luna, Antoni L. Andreu, Jordi Barquinero, Michio Hirano, Yolanda Cámara, and Ramon Martí
Human Gene Therapy, 2016, Volume 27, Number 9, Page 656
Raquel Cabrera-Pérez, Javier Torres-Torronteras, Ferran Vila-Julià, Francisco J Ortega, Yolanda Cámara, Jordi Barquinero, and Ramon Martí
Expert Opinion on Orphan Drugs, 2015, Volume 3, Number 10, Page 1167
Jonghoon Kang and David C. Samuels
Mitochondrion, 2008, Volume 8, Number 2, Page 103
Beatriz Garcia-Diaz, Caterina Garone, Emanuele Barca, Hamed Mojahed, Purification Gutierrez, Giuseppe Pizzorno, Kurenai Tanji, Fernando Arias-Mendoza, Caterina M. Quinzii, and Michio Hirano
Brain, 2014, Volume 137, Number 5, Page 1337
Germaine Escames, Luis Carlos López, José Antonio García, Laura García-Corzo, Francisco Ortiz, and Darío Acuña-Castroviejo
Human Genetics, 2012, Volume 131, Number 2, Page 161
José Marín-García
Vascular Pharmacology, 2010, Volume 52, Number 3-4, Page 120
Ann Saada‐Reisch
Nucleosides, Nucleotides and Nucleic Acids, 2004, Volume 23, Number 8-9, Page 1205
Tally Lerman-Sagie, Esther Leshinsky-Silver, Nathan Watemberg, Yehudit Luckman, and Dorit Lev
Molecular Genetics and Metabolism, 2005, Volume 84, Number 2, Page 127
T. Radivoyevitch, B. Munch-Petersen, L. Wang, and S. Eriksson
Nucleosides, Nucleotides and Nucleic Acids, 2011, Volume 30, Number 3, Page 203
Ann Saada
DNA and Cell Biology, 2004, Volume 23, Number 12, Page 797
Patrick F. Chinnery
Brain, 2007, Volume 130, Number 3, Page 606
Ashraf Virmani, Syed F. Ali, and Zbigniew K. Binienda
Annals of the New York Academy of Sciences, 2010, Volume 1199, Number 1, Page 52
Jana S. Eaton, Z. Ping Lin, Alan C. Sartorelli, Nicholas D. Bonawitz, and Gerald S. Shadel
Journal of Clinical Investigation, 2007, Volume 117, Number 9, Page 2723
Salvia Rodraguez-Mulero, Ekaitz Errasti-Murugarren, Josa Ballaran, Antonio Felipe, Alain Doucet, Fjavier Casado, and Maraal Pastor-Anglada
Kidney International, 2005, Volume 68, Number 2, Page 665

Comments (0)

Please log in or register to comment.
Log in