title: Age-associated decline in mitochondrial respiration and electron transport in Drosophila melanogaster.
abstract: 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.
authors.affiliation: Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Ferguson
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Mockett
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.forename: William C
authors.initials: WC
authors.lastname: Orr
authors.forename: Rajindar S
authors.initials: RS
authors.lastname: Sohal
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D019069:Cell Respiration; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D004579:Electron Transport / Q000502:physiology; D003576:Electron Transport Complex IV / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D018384:Oxidative Stress; D010101:Oxygen Consumption / Q000502:physiology; D013379:Substrate Specificity
chemical_list: D009243:NAD; D005182:Flavin-Adenine Dinucleotide; D006861:Hydrogen Peroxide; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase