The principal objective of the present study was to identify specific alterations in mitochondrial respiratory functions during the aging process. Respiration rates and the activities of electron transport chain complexes were measured at various ages in mitochondria isolated from thoraces of the fruit fly, Drosophila melanogaster, which consist primarily of flight muscles. The rates of state 3 respiration (ADP-stimulated), RCRs (respiratory control ratios) and uncoupled respiration rates decreased significantly as a function of age, using either NAD+- or FAD-linked substrates; however, there were no differences in state 4 respiration (ADP-depleted) rates. There was also a significant age-related decline in the activity of cytochrome c oxidase (complex IV), but not of the other mitochondrial oxidoreductases examined. Exposure of mitochondria isolated from young flies to low doses of KCN or NaAz (sodium azide), complex IV inhibitors, decreased cytochrome c oxidase activity and increased the production of H2O2. Collectively, these results support the hypothesis that impairment of mitochondrial respiration may be a causal factor in the aging process, and that such impairment may result from and contribute to increased H2O2 production in vivo.
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Research Article|
August 23 2005
Age-associated decline in mitochondrial respiration and electron transport in Drosophila melanogaster
Melissa Ferguson;
Melissa Ferguson
*Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, U.S.A.
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Robin J. Mockett;
Robin J. Mockett
*Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, U.S.A.
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Yi Shen;
Yi Shen
*Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, U.S.A.
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William C. Orr;
William C. Orr
†Department of Biological Sciences, Dedman Life Sciences Building, Southern Methodist University, Dallas, TX 75275, U.S.A.
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Rajindar S. Sohal
Rajindar S. Sohal
1
*Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, U.S.A.
1To whom correspondence should be addressed (email sohal@usc.edu).
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Publisher: Portland Press Ltd
Received:
December 22 2004
Revision Received:
April 15 2005
Accepted:
April 25 2005
Accepted Manuscript online:
April 26 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 390 (2): 501–511.
Article history
Received:
December 22 2004
Revision Received:
April 15 2005
Accepted:
April 25 2005
Accepted Manuscript online:
April 26 2005
Citation
Melissa Ferguson, Robin J. Mockett, Yi Shen, William C. Orr, Rajindar S. Sohal; Age-associated decline in mitochondrial respiration and electron transport in Drosophila melanogaster. Biochem J 1 September 2005; 390 (2): 501–511. doi: https://doi.org/10.1042/BJ20042130
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