Yeast lacking superoxide dismutase (s) show elevated levels of “free iron” as measured by whole cell electron paramagnetic resonance
Open accessAbstract
A current hypothesis explaining the toxicity of superoxide anion in vivo is that it oxidizes exposed [4Fe-4S] clusters in certain vulnerable enzymes causing release of iron and enzyme inactivation. The resulting increased levels of "free iron" catalyze deleterious oxidative reactions in the cell. In this study, we used low temperature Fe(III) electron paramagnetic resonance (EPR) spectroscopy to monitor iron status in whole cells of the unicellular eukaryote, Saccharomyces cerevisiae. The experimental protocol involved treatment of the cells with desferrioxamine, a cell-permeant, Fe(III)-specific chelator, to promote oxidation of all of the "free iron" to the Fe(III) state wherein it is EPR-detectable. Using this method, a small amount of EPR-detectable iron was detected in the wild-type strain, whereas significantly elevated levels were found in strains lacking CuZn-superoxide dismutase (CuZn-SOD) (sod1 delta), Mn-SOD (sod2 delta), or both SODs, throughout their growth but particularly in stationary phase. The accumulation was suppressed by expression of wild-type human CuZn-SOD (in the sod1 delta mutant), by pmr1, a genetic suppressor of the sod delta mutant phenotype (in the sod1 delta sod2 delta double knockout strain), and by anaerobic growth. In wild-type cells, an increase in the EPR-detectable iron pool could be induced by treatment with paraquat, a redox-cycling drug that generates superoxide. Cells that were not pretreated with desferrioxamine had Fe(III) EPR signals that were equally as strong as those from treated cells, indicating that "free iron" accumulated in the ferric form in our strains in vivo. Our results indicate a relationship between superoxide stress and iron handling and support the above hypothesis for superoxide-related oxidative damage.
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Iron and hydrogen peroxide are released and may undergo other damaging reactions.
“Iron and hydrogen peroxide are released and may undergo other damaging reactions [114].”
From Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity (2023) · cites this paper as [114]
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- Authors
- Srinivasan, C., Liba, A., Imlay, J. A., Valentine, J. S., & Gralla, E. B.
- Affiliations
- University of California, Los Angeles (US)
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Gralla, Edith Butler
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-09
- Volume
- 275
- Issue
- 38
- Pages
- 29187-29192
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1965668748
- Cited by
- 134
- References
- 54
- Citations by year
- 2026: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 7 · 2014: 7 · 2013: 3 · 2012: 5
- FWCI
- 3.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM59030, R01GM059030)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-46828, R01DK046828)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- superoxide dismutase, free iron, iron accumulation, [4Fe-4S] cluster, Saccharomyces cerevisiae, Cu/Zn superoxide dismutase, Mn superoxide dismutase, deferoxamine, paraquat, oxidative damage, iron homeostasis, anaerobic growth
- MeSH terms
- Electron Spin Resonance Spectroscopy, Humans, Iron, Mutation, Saccharomyces cerevisiae, Superoxide Dismutase, Gene Expression Regulation, Enzymologic
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