title: Ectopic expression of catalase in Drosophila mitochondria increases stress resistance but not longevity.
abstract: The goal of this study was to test the hypothesis that the rate of mitochondrial oxidant production governs the aging process of the fruit fly, Drosophila melanogaster. Catalase, an antioxidative enzyme expressed in the cytosol and peroxisomes of Drosophila, was targetted ectopically to the mitochondrial matrix by fusion of a leader peptide derived from ornithine aminotransferase with its N-terminus. The presence of the transgene encoding this fusion protein was associated with moderate (35 +/- 13%) increases in total catalase activity in most lines, and measurable levels of catalase activity in the mitochondria (30-140 U/mg protein). There was no impact on the life span of the flies at 25 degrees C, even in an exceptional line with a 149% increase in total catalase activity, and there was a small decrease in longevity at 29 degrees C. There were no compensatory changes in the rate of metabolism or physical activity, or in the levels of other major antioxidants, suggesting that the aging process was largely unaffected. Resistance to exogenous hydrogen peroxide, paraquat, and cold stress was enhanced, but there was no appreciable effect on resistance to hyperoxia. The results demonstrate the importance of mitochondrial antioxidant levels in the resistance to oxidative stress at the organismal level, and illustrate that different effects on aging and stress resistance may ensue from a single treatment. The main inferences drawn are that: (i) levels of stress resistance may neither be a cause nor a reliable indicator of the rate of aging, and (ii) bolstering antioxidant levels in Drosophila may not delay or slow down the aging process.
authors.affiliation: Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Mockett
authors.forename: Anne Cécile V
authors.initials: AC
authors.lastname: Bayne
authors.forename: Linda K
authors.initials: LK
authors.lastname: Kwong
authors.forename: William C
authors.initials: WC
authors.lastname: Orr
authors.forename: Rajindar S
authors.initials: RS
authors.lastname: Sohal
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D003080:Cold Temperature; D003600:Cytosol / Q000201:enzymology; D004331:Drosophila melanogaster / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018496:Hyperoxia / Q000378:metabolism; D008136:Longevity / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology; D013312:Stress, Physiological / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D015996:Survival Rate
chemical_list: D000975:Antioxidants; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D010269:Paraquat