Glutathione: a key component of the cytoplasmic labile iron pool
Abstract
The cytoplasmic labile iron pool supplies iron to the mitochondrion for heme and iron sulfur cluster synthesis and to many cytoplasmic enzymes, thereby controlling numerous metabolic reactions. Surprisingly the chemical nature of this pool has never been convincingly characterised. Here we provide evidence for iron(II)glutathione being the dominant component of this pool. We report for the first time the affinity constant for the glutathione-iron(II) interaction and use this value to study the cytoplasmic speciation of iron(II). The formation of this complex is a major determinant of the electrode potential of the cytoplasmic ferrous iron pool, a means of selecting between iron(II) and manganese(II) and it provides a substrate for glutaredoxin/iron clusters at the dimer interface of glutaredoxins involved in the synthesis of Fe-S cluster proteins.
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Among metabolites, the abundant LMW thiol glutathione binds Fe2+ with sufficient affinity to form part of the buffered pool.
“Among metabolites, the abundant LMW thiol glutathione (GSH; l-γ-glutamyl-l-cysteinyl-glycine) binds Fe2+ with sufficient affinity to form part of the buffered pool.143”
From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [143]
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- Authors
- Hider, R. C., & Kong, X. L.
- Affiliations
- King's College London (GB)
- Corresponding author
- Hider, Robert C.
- Venue
- BioMetals
- Published
- 2011-07-17
- Volume
- 24
- Issue
- 6
- Pages
- 1179-1187
- ISSN
- 0966-0844 (ISSN-L)
- 1572-8773
- OpenAlex
- W1965389900
- Cited by
- 281
- References
- 4
- Citations by year
- 2026: 19 · 2025: 22 · 2024: 28 · 2023: 31 · 2022: 18 · 2021: 27 · 2020: 30 · 2019: 14 · 2018: 9 · 2017: 15 · 2016: 11 · 2015: 14 · 2014: 20 · 2013: 10 · 2012: 11
- FWCI
- 8.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- BioMetals (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Keywords
- glutathione, labile iron pool, iron speciation, affinity constant, electrode potential, glutaredoxin, iron-sulfur proteins, heme biosynthesis
- MeSH terms
- Animals, Cytoplasm, Glutathione, Humans, Iron, Ligands, Mitochondria, Models, Molecular, Oxidation-Reduction, Protein Conformation, Sulfhydryl Compounds, Sulfur, Molecular Structure
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