Iron–sulfur cluster biogenesis and trafficking in mitochondria
Open accessAbstract
The biogenesis of iron-sulfur (Fe/S) proteins in eukaryotes is a multistage, multicompartment process that is essential for a broad range of cellular functions, including genome maintenance, protein translation, energy conversion, and the antiviral response. Genetic and cell biological studies over almost 2 decades have revealed some 30 proteins involved in the synthesis of cellular [2Fe-2S] and [4Fe-4S] clusters and their incorporation into numerous apoproteins. Mechanistic aspects of Fe/S protein biogenesis continue to be elucidated by biochemical and ultrastructural investigations. Here, we review recent developments in the pursuit of constructing a comprehensive model of Fe/S protein assembly in the mitochondrion.
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Once inside mitochondria, iron is incorporated into heme and iron-sulfur clusters by frataxin and GLRX5.
“Once inside the organelle the iron is incorporated into heme and iron-sulfur (Fe-S) clusters by frataxin and GLRX5 (Glutaredoxin-related protein 5) (Lill, 2009; Braymer and Lill, 2017).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Braymer and Lill, 2017
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Karmi, O., Marjault, H., Bai, F., Roy, S., Sohn, Y., Darash‐Yahana, M., Morcos, F., Ioannidis, K., Nahmias, Y., Jennings, P. A., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2121491119 · Cited by 51 · see citing works
Mechanisms of cellular iron sensing, regulation of erythropoiesis and mitochondrial iron utilization
Maio, N., Zhang, D., Ghosh, M. C., Jain, A., SantaMaria, A. M., & Rouault, T. A. (2021) · Seminars in Hematology · doi:10.1053/j.seminhematol.2021.06.001 · Cited by 49 · see citing works
Lipotoxic Impairment of Mitochondrial Function in β-Cells: A Review
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Molecular pathophysiology and genetic mutations in congenital sideroblastic anemia
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Regulation of the redox metabolome and thiol proteome by hydrogen sulfide
Kumar, R., & Banerjee, R. V. (2021) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2021.1893641 · Cited by 46 · see citing works
Iron–Sulfur Cluster Biogenesis as a Critical Target in Cancer
Petronek, M. S., Spitz, D. R., & Allen, B. G. (2021) · Antioxidants · doi:10.3390/antiox10091458 · Cited by 46 · see citing works
Wofford, J. D., Bolaji, N., Dziuba, N., Outten, F. W., & Lindahl, P. A. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.005233 · Cited by 47 · see citing works
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Iron Metabolism: An Under Investigated Driver of Renal Pathology in Lupus Nephritis
Wlazlo, E., Mehrad, B., Morel, L. M., & Scindia, Y. M. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.643686 · Cited by 44 · see citing works
Pulling back the mitochondria’s iron curtain
David, S. B. Z., Shkuri, L., & Ast, T. (2025) · npj Metabolic Health and Disease · doi:10.1038/s44324-024-00045-y · Cited by 46 · see citing works
20,000 picometers under the OMM: diving into the vastness of mitochondrial metabolite transport
Cunningham, C. N., & Rutter, J. P. (2020) · EMBO Reports · doi:10.15252/embr.202050071 · Cited by 44 · see citing works
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Characterization of the novel mitochondrial genome segregation factor TAP110 in Trypanosoma brucei
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A pathway for assembling [4Fe‐4S]2+ clusters in mitochondrial iron–sulfur protein biogenesis
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Stehling, O., Jeoung, J., Freibert, S., Paul, V. D., Bänfer, S., Niggemeyer, B., Rösser, R., Dobbek, H., & Lill, R. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1807762115 · Cited by 44 · see citing works
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- Authors
- Braymer, J. J., & Lill, R.
- Affiliations
- Philipps University of Marburg (DE)
- Corresponding author
- Lill, Roland
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 292
- Issue
- 31
- Pages
- 12754-12763
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC5546016
- OpenAlex
- W2625087901
- Cited by
- 389
- References
- 100
- Citations by year
- 2026: 29 · 2025: 29 · 2024: 32 · 2023: 39 · 2022: 45 · 2021: 40 · 2020: 56 · 2019: 44 · 2018: 57 · 2017: 16
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (Koselleck grant, LI 415/5, SFB 987, SPP 1710, and SPP 1927)
- German-Israeli Foundation for Scientific Research and Development (I-1302-412.13/2015)
- H2020 Marie Skłodowska-Curie Actions (659325)
- 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 clusters, mitochondrial iron-sulfur proteins, [2Fe-2S] cluster, [4Fe-4S] cluster, cluster assembly, iron-sulfur proteins, genome maintenance, mRNA translation, energy conversion, antiviral response
- MeSH terms
- Frataxin, Acyl Carrier Protein, Adrenodoxin, Animals, Apoenzymes, Humans, Iron-Sulfur Proteins, Mitochondria, Models, Biological, Models, Molecular, Protein Conformation, Species Specificity, Sulfurtransferases, Gene Expression Regulation, Enzymologic, Protein Folding, Protein Transport, Mitochondrial Proteins, Saccharomyces cerevisiae Proteins, Iron-Binding Proteins, Protein Multimerization
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