Enhanced catabolism of mitochondrial superoxide/hydrogen peroxide and aging in transgenic Drosophila
Open accessAbstract
The generation of superoxide anion radicals (O2*-) and hydrogen peroxide (H2O2) during mitochondrial respiration has been widely postulated to be causally linked to the aging process. The hypothesis that a specific enhancement of mitochondrial O2*-/H2O2 catabolism would delay age-associated physiological changes and extend the lifespan was tested by simultaneous overexpression of MnSOD (manganese superoxide dismutase) and catalase, ectopically targeted to the mitochondrial matrix of transgenic Drosophila melanogaster. The increased activities of these antioxidative enzymes resulted in a decrease of mitochondrial H2O2 release and enhancement of free methionine content. The MnSOD/mitochondrial catalase transgenic flies displayed an enhanced resistance to experimental oxidative stress, induced by dietary H2O2 administration or by exposure to 100% ambient oxygen. However, the lifespan of the flies was decreased, by up to 43%, and this effect coincided with (i) an overall decrease in physical fitness, as measured by the speed of walking, and (ii) an age-related decrease in mitochondrial state 3 (ADP-stimulated) respiration. These findings support the notion that mitochondrial O2*-/H2O2 production at physiological levels is essential for normal biological processes leading to the attainment of a normal lifespan.
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When manganese superoxide dismutase (MnSOD) and catalase are ectopically targeted to the mitochondrial matrix of transgenic flies, lifespan is decreased up to 43%.
“However, when manganese superoxide dismutase (MnSOD) and catalase are ectopically targeted to the mitochondrial matrix of transgenic flies, lifespan is decreased up to 43% (Bayne et al., 2005).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Bayne et al., 2005
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- Authors
- Bayne, A.-C. V., Mockett, R. J., Orr, W. C., & Sohal, R. S.
- Affiliations
- University of Southern California (US)
- Southern Methodist University (US)
- ORCID
- Mockett, Robin J.
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2005-10-10
- Volume
- 391
- Issue
- 2
- Pages
- 277-284
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1276925
- OpenAlex
- W2038473565
- Cited by
- 84
- References
- 51
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 6 · 2019: 1 · 2018: 5 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 6 · 2013: 3 · 2012: 3
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Southern California
- National Institutes of Health (RO1 AG7657)
- National Institute on Aging (RO1 AG7657, R01AG007657)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- mitochondrial superoxide, hydrogen peroxide, aging, lifespan extension, manganese superoxide dismutase, catalase, mitochondrial matrix, oxidative stress resistance, mitochondrial respiration, transgenic Drosophila, antioxidant enzymes
- MeSH terms
- Aging, Animals, Catalase, Drosophila melanogaster, Hydrogen Peroxide, Longevity, Mitochondria, Ornithine-Oxo-Acid Transaminase, Superoxides, Superoxide Dismutase, Gene Expression Regulation, Enzymologic, Oxidative Stress, Animals, Genetically Modified
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