The Interaction of Mitochondrial Iron with Manganese Superoxide Dismutase
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Superoxide dismutase 2 (SOD2) is one of the rare mitochondrial enzymes evolved to use manganese as a cofactor over the more abundant element iron. Although mitochondrial iron does not normally bind SOD2, iron will misincorporate into Saccharomyces cerevisiae Sod2p when cells are starved for manganese or when mitochondrial iron homeostasis is disrupted by mutations in yeast grx5, ssq1, and mtm1. We report here that such changes in mitochondrial manganese and iron similarly affect cofactor selection in a heterologously expressed Escherichia coli Mn-SOD, but not a highly homologous Fe-SOD. By x-ray absorption near edge structure and extended x-ray absorption fine structure analyses of isolated mitochondria, we find that misincorporation of iron into yeast Sod2p does not correlate with significant changes in the average oxidation state or coordination chemistry of bulk mitochondrial iron. Instead, small changes in mitochondrial iron are likely to promote iron-SOD2 interactions. Iron binds Sod2p in yeast mutants blocking late stages of iron-sulfur cluster biogenesis (grx5, ssq1, and atm1), but not in mutants defective in the upstream Isu proteins that serve as scaffolds for iron-sulfur biosynthesis. In fact, we observed a requirement for the Isu proteins in iron inactivation of yeast Sod2p. Sod2p activity was restored in mtm1 and grx5 mutants by depleting cells of Isu proteins or using a dominant negative Isu1p predicted to stabilize iron binding to Isu1p. In all cases where disruptions in iron homeostasis inactivated Sod2p, we observed an increase in mitochondrial Isu proteins. These studies indicate that the Isu proteins and the iron-sulfur pathway can donate iron to Sod2p.
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A molecular cross-talk exists between Mn and Fe in mitochondria, able to switch SOD2 functionality.
“A molecular cross-talk exists between Mn and Fe in mitochondria, able to switch SOD2 functionality [48,49].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [48]
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- Authors
- Naranuntarat, A., Jensen, L. T., Pazicni, S., Penner-Hahn, J. E., & Culotta, V. C.
- Affiliations
- Johns Hopkins University (US)
- University of Michigan (US)
- Corresponding author
- Culotta, Valeria C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 284
- Issue
- 34
- Pages
- 22633-22640
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2755670
- OpenAlex
- W1993779780
- Cited by
- 66
- References
- 49
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 7 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 7
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of New Hampshire Scholars Repository (University of New Hampshire at Manchester) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM-38047, R01GM038047)
- National Institute of Environmental Health Sciences (R01ES008996, P30ES003819, ES08996)
- Topics
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Keywords
- manganese superoxide dismutase, mitochondrial iron, iron-sulfur cluster assembly, MTM1, iron homeostasis, Saccharomyces cerevisiae, iron binding, mitochondrial iron homeostasis
- MeSH terms
- Superoxide Dismutase 2, Iron, Mitochondria, Mutation, Protein Binding, Saccharomyces cerevisiae, Superoxide Dismutase, Immunoblotting, Absorptiometry, Photon, Gene Expression Regulation, Fungal, ATP-Binding Cassette Transporters, HSP70 Heat-Shock Proteins, Mitochondrial Proteins, Saccharomyces cerevisiae Proteins, Glutaredoxins
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