Oxidative stress and aging reduce cox I RNA and cytochrome oxidase activity in Drosophila

Steven R. Schwarze, Richard Weindruch, Judd M. Aiken

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Drosophila melanogaster displays an age-associated increase in oxidative damage and a decrease in mitochondrial transcripts. To determine if these changes result in energy production deficiencies, we measured the electron transport system (ETS) enzyme activity, and ATP levels with age. No statistically significant influences of age on activities of complexes I and II or citrate synthase were observed. In contrast, from 2 to 45 days post- eclosion, declines were found in complex IV cytochrome c oxidase activity (COX, 40% decline) and ATP abundance (15%), while lipid peroxidation increased 71%. We next examined flies that were either genetically or chemically oxidatively stressed to determine the effect on levels of mitochondrial-encoded cytochrome oxidase I RNA (coxI) and COX activity. A catalase null mutant line had 48% of coxI RNA compared to the wild type. In Cu/Zn superoxide dismutase (cSOD) null flies, the rate of coxI RNA decline was greater than in controls. CoxI RNA also declined with increasing hydrogen peroxide (H2O2) treatment, which was reflected in reduced cytochrome c oxidase (COX) activity. These results show that oxidative stress is closely associated with reductions in mitochondrial transcript levels and support the hypothesis that oxidative stress may contribute to mitochondrial dysfunction and aging in D. melanogaster.

Original languageEnglish
Pages (from-to)740-747
Number of pages8
JournalFree Radical Biology and Medicine
Volume25
Issue number6
DOIs
StatePublished - Oct 1998

Bibliographical note

Funding Information:
We thank Dr. James Mahaffey (North Carolina State University) for providing the catalase fly lines, Dr. John Phillips (University of Guelph) for providing the cSOD fly lines, and Dr. Debbie McKenzie for the helpful criticism of this manuscript. This work was supported by NIH grants RO1 AG11604 and NIH training grant T32 AG00213. This is publication 98-05 from the Madison VA-GRECC.

Keywords

  • ATP
  • Aging
  • Catalase
  • Cytochrome oxidase
  • Drosophila
  • Free radical
  • Mitochondria
  • Mitochondrial RNA
  • Superoxide dismutase

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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