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Structural determinants in human DNA polymerase gamma account for mitochondrial toxicity from nucleoside analogs.

Author: CopelandWilliam C, LimSusan E, LongleyMatthew J, PonamarevMikhail V

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Overview

Antiviral nucleoside analog therapy successfully delays progression of HIV infection to AIDS, but these drugs cause unwelcome side-effects by inducing mitochondrial toxicity. We explored the role of three highly conserved amino acid residues in the active site of human pol gamma that modulate selection of nucleotide analogs as substrates for incorporation.
Paper Details　
Original Abstract of the Article :
Although antiviral nucleoside analog therapy successfully delays progression of HIV infection to AIDS, these drugs cause unwelcome side-effects by inducing mitochondrial toxicity. We and others have demonstrated that the mitochondrial polymerase, DNA polymerase gamma (pol gamma), participates in mit...See full text at original site
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引用元：
https://doi.org/10.1016/s0022-2836(03)00405-4

データ提供：米国国立医学図書館（NLM）

Unlocking the Secrets of Mitochondrial Toxicity: A Molecular Investigation

Antiviral nucleoside analogs have revolutionized the treatment of HIV infection, but they can also cause mitochondrial toxicity, a serious side effect that can affect the function of our cells' energy factories. This study delves into the molecular mechanisms underlying mitochondrial toxicity, focusing on the role of DNA polymerase gamma (pol gamma), a key enzyme involved in DNA replication within mitochondria.

Researchers conducted a series of experiments, carefully analyzing the activity of pol gamma in the presence of different nucleoside analogs. It's like exploring a hidden chamber in a desert pyramid, meticulously examining the intricate workings of a complex mechanism.

Pol Gamma: A Gatekeeper of Mitochondrial Health

The study revealed that pol gamma plays a crucial role in incorporating antiviral nucleoside analogs into mitochondrial DNA. It's like a gatekeeper at the entrance to a desert city, deciding which travelers are allowed to enter. The study identified specific amino acid residues in pol gamma that influence the incorporation of these analogs, providing insights into the molecular basis of mitochondrial toxicity.

Navigating the Landscape of Mitochondrial Toxicity

This research provides valuable insights into the complex interplay between antiviral drugs and mitochondrial function. It's like mapping a desert landscape, uncovering pathways that can lead to both beneficial and detrimental outcomes. The findings could potentially guide the development of new antiviral drugs with reduced mitochondrial toxicity.

Dr.Camel's Conclusion

This research sheds light on the molecular mechanisms underlying mitochondrial toxicity caused by antiviral nucleoside analogs. It's like uncovering the secrets of a hidden oasis in the desert, revealing the intricate pathways that influence the well-being of the desert's inhabitants. The findings offer valuable insights for developing new antiviral drugs with improved safety profiles, minimizing the risk of mitochondrial damage and enhancing the effectiveness of HIV treatment.

Date :
  1. Date Completed 2003-06-19
  2. Date Revised 2019-07-10
Further Info :

Pubmed ID

12742017

DOI: Digital Object Identifier

10.1016/s0022-2836(03)00405-4

SNS
PICO Info
in preparation
Languages

English

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