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Titolo:
The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals
Autore:
Dolce, V; Fiermonte, G; Runswick, MJ; Palmieri, F; Walker, JE;
Indirizzi:
Univ Bari, Dept Pharmacobiol, Biochem & Mol Biol Lab, I-70125 Bari, Italy Univ Bari Bari Italy I-70125 Biochem & Mol Biol Lab, I-70125 Bari, Italy Univ Calabria, Dept Pharmacobiol, Biochem & Mol Biol Lab, I-87036 Cosenza,Italy Univ Calabria Cosenza Italy I-87036 Mol Biol Lab, I-87036 Cosenza,Italy MRC, Dunn Human Nutr Unit, Cambridge CB2 2XY, England MRC Cambridge England CB2 2XY uman Nutr Unit, Cambridge CB2 2XY, England
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 5, volume: 98, anno: 2001,
pagine: 2284 - 2288
SICI:
0027-8424(20010227)98:5<2284:THMDCA>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
BACTERIAL EXPRESSION; BOVINE MITOCHONDRIA; DIDANOSINE DDI; YEAST; DNA; RECONSTITUTION; IDENTIFICATION; TRANSPORTER; ZIDOVUDINE; PHOSPHORYLATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Palmieri, F Univ Bari, Dept Pharmacobiol, Biochem & Mol Biol Lab, Via E Orabona 4, I-70125 Bari, Italy Univ Bari Via E Orabona 4 Bari Italy I-70125 0125 Bari, Italy
Citazione:
V. Dolce et al., "The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals", P NAS US, 98(5), 2001, pp. 2284-2288

Abstract

The synthesis of DNA in mitochondria requires the uptake of deoxynucleotides into the matrix of the organelle. We have characterized a human cDNA encoding a member of the family of mitochondrial carriers. The protein has been overexpressed in bacteria and reconstituted into phospholipid vesicles where it catalyzed the transport of all four deoxy (d) NDPs, and, less efficiently, the corresponding dNTPs, in exchange for dNDPs, ADP, or ATP. It did not transport dNMPs, NMPs, deoxynucleosides, nucleosides, purines, or pyrimidines. The physiological role of this deoxynucleotide carrier is probably to supply deoxynucleotides to the mitochondrial matrix for conversion to triphosphates and incorporation into mitochondrial DNA. The protein is expressed in all human tissues that were examined except for placenta, in accord with such a central role. The deoxynucleotide carrier also transports dideoxynucleotides efficiently. It is likely to be medically important by providing the means of uptake into mitochondria of nucleoside analogs, leading tothe mitochondrial impairment that underlies the toxic side effects of suchdrugs in the treatment of viral illnesses, including AIDS, and in cancer therapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 15:22:50