The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Role of Human Mitochondrial Nfs1 in Cytosolic Iron-Sulfur Protein Biogenesis and Iron Regulation
Abstract
The biogenesis of iron-sulfur (Fe/S) proteins in eukaryotes is a complex process involving more than 20 components. So far, functional investigations have mainly been performed in Saccharomyces cerevisiae. Here, we have analyzed the role of the human cysteine desulfurase Nfs1 (huNfs1), which serves as a sulfur donor in biogenesis. The protein is located predominantly in mitochondria, but small amounts are present in the cytosol/nucleus. huNfs1 was depleted efficiently in HeLa cells by a small interfering RNA (siRNA) approach, resulting in a drastic growth retardation and striking morphological changes of mitochondria. The activities of both mitochondrial and cytosolic Fe/S proteins were strongly impaired, demonstrating that huNfs1 performs an essential function in Fe/S protein biogenesis in human cells. Expression of murine Nfs1 (muNfs1) in huNfs1-depleted cells restored both growth and Fe/S protein activities to wild-type levels, indicating the specificity of the siRNA depletion approach. No complementation of the growth retardation was observed, when muNfs1 was synthesized without its mitochondrial presequence. This extramitochondrial muNfs1 did not support maintenance of Fe/S protein activities, neither in the cytosol nor in mitochondria. In conclusion, our study shows that the essential huNfs1 is required inside mitochondria for efficient maturation of cellular Fe/S proteins. The results have implications for the regulation of iron homeostasis by cytosolic iron regulatory protein 1.
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In the citing paper
“NFS1 harvests sulfur from cysteine for the biogenesis of ISCs (27)”
From Eprenetapopt triggers ferroptosis, inhibits NFS1 cysteine desulfurase, and synergizes with serine and glycine dietary restriction (2022) · cites this paper as [27]
In the citing paper
“The sulfur is provided by NFS1, a cysteine desulfurase which removes a sulfur moiety from L-cysteine (Biederbick et al., 2006).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Biederbick et al., 2006
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Cites
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“Most of the 14 known mitochondrial ISC proteins exhibit sequence similarities to bacterial proteins encoded by the isc operon which is crucial for Fe/S cluster assembly in bacteria (7, 22, 55).”
BackgroundThe mitochondrial proteins Atm1p and Nfs1p are essential for biogenesis of cytosolic Fe/S proteins
Kispál, G., Csere, P., Prohl, C., & Lill, R. (1999) · The EMBO Journal · doi:10.1093/emboj/18.14.3981 · Cited by 699
Self-citationAssembly of Iron-Sulfur Clusters
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Cysteine desulfurase activity indicates a role for NIFS in metallocluster biosynthesis.
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Function and biogenesis of iron-sulphur proteins
Lill, R. (2009) · Nature · doi:10.1038/nature08301 · Cited by 1,167
Self-citationRegulation of cellular iron metabolism
Wang, J., & Pantopoulos, K. (2011) · Biochemical Journal · doi:10.1042/bj20101825 · Cited by 986
Maturation of Iron-Sulfur Proteins in Eukaryotes: Mechanisms, Connected Processes, and Diseases
Lill, R., & Mühlenhoff, U. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.052705.162653 · Cited by 605
Self-citationThe role of mitochondria in cellular iron–sulfur protein biogenesis and iron metabolism
Lill, R., Hoffmann, B., Molik, S., Pierik, A. J., Rietzschel, N., Stehling, O., Uzarska, M. A., Webert, H., Wilbrecht, C., & Mühlenhoff, U. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.05.009 · Cited by 513
Self-citationMechanisms of Mitochondrial Iron-Sulfur Protein Biogenesis
Lill, R., & Freibert, S.-A. (2020) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-013118-111540 · Cited by 453
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Metadata
- Authors
- Biederbick, A., Stehling, O., Rösser, R., Niggemeyer, B., Nakai, Y., Elsässer, H.-P., & Lill, R.
- Affiliations
- Philipps University of Marburg (DE)
- Institut für Zytobiologie, Philipps Universität Marburg
- Osaka Medical and Pharmaceutical University (JP)
- Corresponding author
- Lill, Roland
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2006-08-01
- Volume
- 26
- Issue
- 15
- Pages
- 5675-5687
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2143602831
- Cited by
- 164
- References
- 56
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 6 · 2018: 12 · 2017: 14 · 2016: 6 · 2015: 7 · 2014: 10 · 2013: 14 · 2012: 9
- FWCI
- 7.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Metalloenzymes and iron-sulfur proteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- NFS1, cysteine desulfurase, mitochondrial iron-sulfur proteins, iron homeostasis, iron regulatory protein 1, mitochondrial morphology, human cells, mitochondrial presequence
- MeSH terms
- Amino Acid Sequence, Animals, Cytosol, Genetic Vectors, HeLa Cells, Homeostasis, Humans, Iron, Iron-Sulfur Proteins, Mitochondria, Molecular Sequence Data, Carbon-Sulfur Lyases, Sulfurtransferases, Sequence Alignment, Mitochondrial Proteins, Saccharomyces cerevisiae Proteins, RNA, Small Interfering, Mice
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