Identification of a novel mitochondrial dNTP carrier and its interaction with anti-HIV nucleoside analogs (Meeting abstract).

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Identification of a novel mitochondrial dNTP carrier and its interaction with anti-HIV nucleoside analogs (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 38:A414 1997. Unique Identifier : AIDSLINE MED/97620923
Bridges EG; Jiang ZL; Cheng YC; Yale University School of Medicine, New Haven, CT 06410

Abstract: Recent clinical and laboratory findings suggest damage to mitochondrial function as a mechanism of toxicity of antiviral nucleoside analog (nsa's). Though mitochondria contain kinases that can phosphorylate nucleosides, our previous studies suggest the nsa-triphosphates (nsa-TPs) that inhibit mitochondrial DNA replication are produced in the cytoplasm and transported into mitochondria. Using photolabeling to study this novel mitochondrial carrier, a unique 29 kD mitochondrial polypeptide was identified. Using 32P-labeled nucleotides, the 29 kD protein was photolabeled by dCTP, TTP, and dGTP but not by ATP or dATP. When reconstituted into an artificial liposome system, a unique mitochondrial carrier activity capable of dNTP transport was observed. The results show that TTP and dCTP are the major transport substrates. Substrate competition experiments show that TTP and dCTP transport could be inhibited by the di- and tri-phosphates of deoxycytidine or thymidine but not by monophosphates, nucleosides, or bases. In addition, this dNTP carrier activity was not inhibited by specific ATP/ADP translocase inhibitors. This evidence supports a model in which dNTP's and nsa-TPs can move across the mitochondrial membrane on a novel carrier and represents a unique mitochondrial process common to all nsa's that may play an important role in their mechanism of toxicity.

Keywords: *Anti-HIV Agents/METABOLISM *Carrier Proteins/METABOLISM *Mitochondria/METABOLISM *Nucleotides/METABOLISM
971130
M97B1216

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1997. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1997. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .