DNA Precursor Metabolism and Mitochondrial Genome Stability

Abstract

This project investigated DNA precursor metabolism in mammalian mitochondria, attempting to define relationships between deoxyribonucleoside triphosphate (dNTP) metabolism and mutagenesis in the mitochondrial genome. Specific contributions include: (1) We found that conditions altering the normal balance among the four dNTP pools within the mitochondrion stimulate both point and deletion mutagenesis; (2) dNTP pools in mitochondria from some tissues are highly asymmetric contributes toward the elevation of mitochondrial mutation rates compared to nuclear muation rates; (3) Mitochondrial dNTP pools do not show significant age-related changes in the rat, ruling out such changes as causative agents in aging-related accumulation of mitochondrial mutations; (4) A protein previously identified as a mitochondrial deoxyribmucleotide carrier, responsible for dNTP uptake into mitochondria, plays a quite different metablic role; (5) Mammalian mitochondria contain a novel ribonucleotide reductase, which may play a sinificant role in mitochondrial dNTP synthesis.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2003
Accession Number
ADA460347

Entities

People

  • Christopher K. Mathews

Organizations

  • Oregon State University

Tags

Communities of Interest

  • Energy and Power Technologies
  • Human Systems

DTIC Thesaurus Topics

  • Abstracts
  • Carrier Proteins
  • Cells
  • Diseases And Disorders
  • Energy Production
  • Heart
  • Medical Personnel
  • Metabolism
  • Mitochondria
  • Nucleosides
  • Nucleotides
  • Proteins
  • Skeletal Muscle
  • Thiamine Pyrophosphate
  • Thymidines
  • Tissues

Fields of Study

  • Biology
  • Computer science

Readers

  • Molecular Genetics
  • Molecular and Cellular Biology