Hypersensitivity to oxygen and shortened lifespan in a Drosophila mitochondrial complex II mutant
Open accessAbstract
Oxidative stress is implicated as a major cause of aging and age-related diseases, such as Parkinson's and Alzheimer's, as well as ischemia-reperfusion injury in stroke. The mitochondrial electron transport chain is the principal source of reactive oxygen species within cells. Despite considerable medical interest, the molecular mechanisms that regulate reactive oxygen species formation within the mitochondrion remain poorly understood. Here, we report the isolation and characterization of a Drosophila mutant with a defect in subunit b of succinate dehydrogenase (SDH; mitochondrial complex II). The sdhB mutant is hypersensitive to oxygen and displays hallmarks of a progeroid syndrome, including early-onset mortality and age-related behavioral decay. Pathological analysis of the flight muscle, which is amongst the most highly energetic tissues in the animal kingdom, reveals structural abnormalities in the mitochondria. Biochemical analysis shows that, in the mutant, there is a complex II-specific respiratory defect and impaired complex II-mediated electron transport, although the other respiratory complexes remain functionally intact. The complex II defect is associated with an increased level of mitochondrial hydrogen peroxide production, suggesting a possible mechanism for the observed sensitivity to elevated oxygen concentration and the decreased lifespan of the mutant fly.
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In C. elegans and Drosophila, mutations within the same SDH complex produce accelerated ageing.
“Interestingly, in lower organisms such as C. elegans and Drosophila melanogaster, mutations within the same SDH complex can produce an accelerated ageing phenotype 97, 98 .”
From The common biology of cancer and ageing (2007) · cites this paper as [98]
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- Authors
- Walker, D. W., Hájek, P., Muffat, J., Knoepfle, D., Cornelison, S., Attardi, G., & Benzer, S.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- Benzer, Seymour
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-10-31
- Volume
- 103
- Issue
- 44
- Pages
- 16382-16387
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2055486023
- Cited by
- 105
- References
- 26
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 7 · 2016: 3 · 2015: 4 · 2014: 9 · 2013: 8 · 2012: 9
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- National Science Foundation
- Ellison Medical Foundation
- University of Washington
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- succinate dehydrogenase, lifespan, aging, oxidative stress, reactive oxygen species, hydrogen peroxide, electron transport chain, progeroid syndromes, Drosophila
- MeSH terms
- Aging, Animals, Drosophila melanogaster, Electron Transport, Male, Microscopy, Electron, Mitochondria, Muscles, Mutation, Oxygen, Respiration, Reactive Oxygen Species, Protein Subunits, Electron Transport Complex II
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