Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells
Open accessAbstract
Iron-sulfur (Fe-S) clusters are cofactors found in many proteins that have important redox, catalytic or regulatory functions. In mammalian cells, almost all known Fe-S proteins are found in the mitochondria, but at least one is found in the cytosol. Here we report cloning of the human homologs to IscU and NifU, iron-binding proteins that play a critical role in Fe-S cluster assembly in bacteria. In human cells, alternative splicing of a common pre-mRNA results in synthesis of two proteins that differ at the N-terminus and localize either to the cytosol (IscU1) or to the mitochondria (IscU2). Biochemical analyses demonstrate that IscU proteins specifically associate with IscS, a cysteine desulfurase that is proposed to sequester inorganic sulfur for Fe-S cluster assembly. Protein complexes containing IscU and IscS can be found in the mitochondria as well as in the cytosol, implying that Fe-S cluster assembly takes place in multiple subcellular compartments in mammalian cells. The possible roles of the IscU proteins in mammalian cells and the potential implications of compartmentalization of Fe-S cluster assembly are discussed.
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Mitochondrial iron is required for the synthesis of Fe-S clusters, and their biogenesis is thought to be one of the most important functions of mitochondria.
“Mitochondrial iron is also required for the synthesis of Fe-S clusters and indeed their biogenesis is thought to be one of the most important functions of the mitochondria—even though some Fe-S assembly can occur in the cytosol and nucleus (Tong, 2000; Tong et al., 2003; Tong and Rouault, 2006).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Tong, 2000
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BackgroundThe Role of Iron Regulation in Immunometabolism and Immune-Related Disease
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- Authors
- Tong, W., & Rouault, T.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Rouault, Tracey
- Venue
- The EMBO Journal
- Published
- 2000-11-01
- Volume
- 19
- Issue
- 21
- Pages
- 5692-5700
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC305809
- OpenAlex
- W2006178088
- Cited by
- 194
- References
- 34
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 13 · 2016: 9 · 2015: 3 · 2014: 6 · 2013: 9 · 2012: 7
- FWCI
- 11.54
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- iron-sulfur cluster assembly, IscU, NifU, IscS, cysteine desulfurase, alternative splicing, mitochondrial iron-sulfur proteins, subcellular compartmentalization, human cells, protein complex formation
- MeSH terms
- Amino Acid Sequence, Animals, Bacterial Proteins, Base Sequence, Cell Compartmentation, Cloning, Molecular, Cytosol, DNA, Humans, Iron-Sulfur Proteins, Mitochondria, Molecular Sequence Data, Carbon-Sulfur Lyases, Transfection, Gene Expression, Sequence Homology, Amino Acid, Alternative Splicing, COS Cells, Escherichia coli Proteins
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