Probing in vivo Mn 2+ speciation and oxidative stress resistance in yeast cells with electron-nuclear double resonance spectroscopy
Open accessAbstract
Manganese is an essential transition metal that, among other functions, can act independently of proteins to either defend against or promote oxidative stress and disease. The majority of cellular manganese exists as low molecular-weight Mn 2+ complexes, and the balance between opposing “essential” and “toxic” roles is thought to be governed by the nature of the ligands coordinating Mn 2+ . Until now, it has been impossible to determine manganese speciation within intact, viable cells, but we here report that this speciation can be probed through measurements of 1 H and 31 P electron-nuclear double resonance (ENDOR) signal intensities for intracellular Mn 2+ . Application of this approach to yeast ( Saccharomyces cerevisiae ) cells, and two pairs of yeast mutants genetically engineered to enhance or suppress the accumulation of manganese or phosphates, supports an in vivo role for the orthophosphate complex of Mn 2+ in resistance to oxidative stress, thereby corroborating in vitro studies that demonstrated superoxide dismutase activity for this species.
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Substantial cytosolic pools of Mn2+ in complex with phosphate and other low molecular weight ligands are also observed in the model yeast Saccharomyces cerevisiae.
“The presence of substantial cytosolic pools of Mn2+ in complex with phosphate and other low molecular weight ligands is also observed in the model yeast Saccharomyces cerevisiae.117”
From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [117]
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Global analysis of protein expression in yeast
Ghaemmaghami, S., Huh, W.-K., Bower, K., Howson, R. W., Belle, A., Dephoure, N., O'Shea, E. K., & Weissman, J. S. (2003) · Nature · doi:10.1038/nature02046 · Cited by 3,750 · see citing works
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Research works printed but not linked: 4
- [2]Wieghardt K (1989) The active sites in manganese-containing metalloproteins and inorganic model complexes. Angewandte Chemie International Edition in English 28:1153 -1172.
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Superoxide dismutases and superoxide reductases
Sheng, Y., Abreu, I. A., Cabelli, D. E., Maroney, M. J., Miller, A.-F., Teixeira, M., & Valentine, J. S. (2014) · Chemical Reviews · doi:10.1021/cr4005296 · Cited by 1,081 · see citing works
Self-citationMetals in Motion: Understanding Labile Metal Pools in Bacteria
Helmann, J. D. (2025) · Biochemistry · doi:10.1021/acs.biochem.4c00726 · Cited by 49 · see citing works
- Authors
- McNaughton, R. L., Reddi, A. R., Clement, M. H. S., Sharma, A., Barnese, K., Rosenfeld, L., Gralla, E. B., Valentine, J. S., Culotta, V. C., & Hoffman, B. M.
- Affiliations
- Northwestern University (US)
- Johns Hopkins University (US)
- University of California, Los Angeles (US)
- Ewha Womans University (KR)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-08-11
- Volume
- 107
- Issue
- 35
- Pages
- 15335-15339
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2932569
- OpenAlex
- W2149160678
- Cited by
- 125
- References
- 1
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 8 · 2022: 7 · 2021: 3 · 2020: 9 · 2019: 11 · 2018: 2 · 2017: 12 · 2016: 3 · 2015: 10 · 2014: 11 · 2013: 12 · 2012: 10
- FWCI
- 5.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Johns Hopkins University
- Korea Science and Engineering Foundation (R31-2008-000-10010-0)
- National Institutes of Health (HL 1353 1)
- National Heart, Lung, and Blood Institute (HL13531, R01HL013531)
- National Institute of General Medical Sciences (R01GM050016, GM50016, F32GM093550, R37GM050016)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-46828, R01DK046828)
- National Institute of Environmental Health Sciences (ES 07141, R01ES008996, P30ES003819, ES08996, T32ES007141)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Electron Spin Resonance Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Keywords
- manganese speciation, Mn2+ complexes, oxidative stress resistance, Saccharomyces cerevisiae, ENDOR spectroscopy, superoxide dismutase activity, manganese toxicity
- MeSH terms
- Algorithms, Electron Spin Resonance Spectroscopy, Homeostasis, Kinetics, Manganese, Models, Chemical, Mutation, Oxygen, Phosphates, Saccharomyces cerevisiae, Spectrophotometry, Atomic, Superoxide Dismutase, Oxidative Stress
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