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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NFS1 harvests sulfur from cysteine for the biogenesis of iron-sulfur clusters.
“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]
The sulfur for Fe-S clusters is provided by NFS1, a cysteine desulfurase.
“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
Cites
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
Brummelkamp, T. R., Bernards, R., & Agami, R. (2002) · Science · doi:10.1126/science.1068999 · Cited by 4,295 · see citing works
Hentze, M. W., Muckenthaler, M. U., & Andrews, N. C. (2004) · Cell · doi:10.1016/s0092-8674(04)00343-5 · Cited by 1,736 · see citing works
Structure, function, and formation of biological iron-sulfur clusters
Johnson, D. C., Dean, D. R., Smith, A. D., & Johnson, M. K. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133518 · Cited by 1,438 · cited 3× · see citing works
“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 · see citing works
Self-citationAssembly of Iron-Sulfur Clusters
Zheng, L., Cash, V. L., Flint, D. H., & Dean, D. R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.21.13264 · Cited by 650 · see citing works
Developmentally Regulated Mitochondrial Fusion Mediated by a Conserved, Novel, Predicted GTPase
Hales, K. G., & Fuller, M. T. (1997) · Cell · doi:10.1016/s0092-8674(00)80319-0 · Cited by 611 · see citing works
Cysteine desulfurase activity indicates a role for NIFS in metallocluster biosynthesis.
Zheng, L., White, R. H., Cash, V. L., Jack, R. F., & Dean, D. R. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.7.2754 · Cited by 597 · see citing works
Iron Metabolism and the IRE/IRP Regulatory System: An Update
Pantopoulos, K. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1306.001 · Cited by 505 · see citing works
Müllner, E. W., Neupert, B., & Kühn, L. C. (1989) · Cell · doi:10.1016/0092-8674(89)90851-9 · Cited by 497 · see citing works
Iron–sulphur cluster biogenesis and mitochondrial iron homeostasis
Rouault, T. A., & Tong, W.-H. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1620 · Cited by 432 · see citing works
Mechanism for the Desulfurization of L-Cysteine Catalyzed by the nifS Gene Product
Zheng, L., White, R. H., Cash, V. L., & Dean, D. R. (1994) · Biochemistry · doi:10.1021/bi00181a031 · Cited by 395 · see citing works
Mühlenhoff, U., Gerber, J., Richhardt, N., & Lill, R. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg446 · Cited by 383 · see citing works
Self-citationMaturation of cellular Fe–S proteins: an essential function of mitochondria
Lill, R., & Kispal, G. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01589-9 · Cited by 358 · see citing works
Self-citationIron–sulfur-protein biogenesis in eukaryotes
Lill, R., & Mühlenhoff, U. (2005) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2005.01.006 · Cited by 333 · see citing works
Self-citationMaturation of cellular Fe-S proteins: an essential function of mitochondria
Gray, H. B. (2000) · Cited by 307 · see citing works
Schwartz, C. J., Djaman, O., Imlay, J. A., & Kiley, P. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.160261497 · Cited by 301 · see citing works
Tong, W.-H., & Rouault, T. A. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.003 · Cited by 294 · see citing works
A mitochondrial ferredoxin is essential for biogenesis of cellular iron-sulfur proteins
Lange, H., Kaut, A., Kispál, G., & Lill, R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.3.1050 · Cited by 272 · see citing works
Self-citationRutherford, J. C., Ojeda, L. D., Balk, J., Mühlenhoff, U., Lill, R., & Winge, D. R. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413731200 · Cited by 242 · see citing works
Self-citationThe Nfs1 interacting protein Isd11 has an essential role in Fe/S cluster biogenesis in mitochondria
Adam, A. C., Bornhövd, C., Prokisch, H., Neupert, W., & Hell, K. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600905 · Cited by 240 · see citing works
Enzymatic activation of sulfur for incorporation into biomolecules in prokaryotes
Kessler, D. (2006) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2006.00036.x · Cited by 239 · see citing works
Umeda, N., Suzuki, T., Yukawa, M., Ohya, Y., Shindo, H., Watanabe, K., & Suzuki, T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409306200 · Cited by 230 · see citing works
Biogenesis of Fe-S Cluster by the Bacterial Suf System
Loiseau, L., de Choudens, S. O., Nachin, L., Fontecave, M., & Barras, F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305953200 · Cited by 226 · see citing works
Essential role of Isd11 in mitochondrial iron–sulfur cluster synthesis on Isu scaffold proteins
Wiedemann, N., Urzica, E. I., Guiard, B., Müller, H., Lohaus, C., Meyer, H. E., Ryan, M. T., Meisinger, C., Mühlenhoff, U., Lill, R., et al. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600906 · Cited by 224 · see citing works
Self-citationApproaches for chemically synthesized siRNA and vector‐mediated RNAi
Amarzguioui, M., Rossi, J. J., & Kim, D.-H. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.08.070 · Cited by 222 · see citing works
Pondarré, C., Antiochos, B., Campagna, D. R., Clarke, S. L., Greer, E. L., Deck, K. M., McDonald, A. A., Han, A., Medlock, A. E., Kutok, J. L., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl012 · Cited by 208 · see citing works
Balk, J., Pierik, A. J., Netz, D. J. A., Mühlenhoff, U., & Lill, R. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600216 · Cited by 206 · see citing works
Self-citationChen, O. S., Crisp, R. J., Valachovic, M., Bard, M., Winge, D. R., & Kaplan, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403209200 · Cited by 202 · see citing works
Li, J., Kogan, M., Knight, S. A. B., Pain, D., & Dancis, A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.46.33025 · Cited by 201 · see citing works
Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells
Tong, W., & Rouault, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5692 · Cited by 194 · see citing works
Tong, W.-H., Jameson, G. N. L., Huynh, B. H., & Rouault, T. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1732541100 · Cited by 194 · see citing works
Land, T., & Rouault, T. A. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80295-6 · Cited by 180 · see citing works
Iron–sulfur protein maturation in human cells: evidence for a function of frataxin
Stehling, O., Elsässer, H.-P., Brückel, B., Mühlenhoff, U., & Lill, R. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh324 · Cited by 176 · see citing works
Self-citationMechanisms of iron–sulfur protein maturation in mitochondria, cytosol and nucleus of eukaryotes
Lill, R., Dutkiewicz, R., Elsässer, H., Hausmann, A., Netz, D. J. A., Pierik, A. J., Stehling, O., Urzica, E. I., & Mühlenhoff, U. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.05.011 · Cited by 170 · see citing works
Self-citationHausmann, A., Netz, D. J. A., Balk, J., Pierik, A. J., Mühlenhoff, U., & Lill, R. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406447102 · Cited by 166 · see citing works
Self-citationA novel eukaryotic factor for cytosolic Fe–S cluster assembly
Roy, A., Solodovnikova, N., Nicholson, T., Antholine, W. E., & Walden, W. E. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg455 · Cited by 160 · see citing works
Involvement of Heme Regulatory Motif in Heme-Mediated Ubiquitination and Degradation of IRP2
Ishikawa, H., Kato, M., Hori, H., Ishimori, K., Kirisako, T., Tokunaga, F., & Iwaï, K. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.05.027 · Cited by 155 · see citing works
Kaiser, J. T., Clausen, T., Bourenkow, G., Bartunik, H. D., Steinbacher, S., & Huber, R. (2000) · Journal of Molecular Biology · doi:10.1006/jmbi.2000.3581 · Cited by 146 · see citing works
[3] Aconitases: A class of metalloproteins highly sensitive to nitric oxide synthesis
Drapier, J., & Hibbs, J. B. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)69006-5 · Cited by 145 · see citing works
Oxygen and Iron Regulation of Iron Regulatory Protein 2
Hanson, E. S., Rawlins, M. L., & Leibold, E. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302798200 · Cited by 140 · see citing works
Yeast Nfs1p Is Involved in Thio-modification of Both Mitochondrial and Cytoplasmic tRNAs
Nakai, Y., Umeda, N., Suzuki, T., Nakai, M., Hayashi, H., Watanabe, K., & Kagamiyama, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312448200 · Cited by 140 · see citing works
Self-citationMühlenhoff, U., Balk, J., Richhardt, N., Kaiser, J. T., Sipos, K., Kispál, G., & Lill, R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406516200 · Cited by 129 · see citing works
Self-citationCharacterization and Expression of Iron Regulatory Protein 2 (IRP2)
Guo, B., Brown, F. M., Phillips, J. D., Yu, Y., & Leibold, E. A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.28.16529 · Cited by 129 · see citing works
Balk, J., Netz, D. J. A., Tepper, K., Pierik, A. J., & Lill, R. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.24.10833-10841.2005 · Cited by 129 · see citing works
Self-citationGilkerson, R., Margineantu, D. H., Capaldi, R., & Selker, J. M. L. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01527-1 · Cited by 122 · see citing works
Adrenodoxin Reductase Homolog (Arh1p) of Yeast Mitochondria Required for Iron Homeostasis
Li, J., Saxena, S., Pain, D., & Dancis, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007198200 · Cited by 119 · see citing works
Wang, J., Chen, G., Muckenthaler, M. U., Galy, B., Hentze, M. W., & Pantopoulos, K. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.3.954-965.2004 · Cited by 116 · see citing works
Gerber, J., Neumann, K., Prohl, C., Mühlenhoff, U., & Lill, R. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.11.4848-4857.2004 · Cited by 115 · see citing works
Self-citationHow Escherichia coli and Saccharomyces cerevisiae Build Fe/S Proteins
Barras, F., Loiseau, L., & Py, B. (2005) · Advances in microbial physiology/Advances in Microbial Physiology · doi:10.1016/s0065-2911(05)50002-x · Cited by 111 · see citing works
Nuclear Localization of Yeast Nfs1p Is Required for Cell Survival
Nakai, Y., Nakai, M., Hayashi, H., & Kagamiyama, H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007878200 · Cited by 86 · see citing works
Self-citationAcquaviva, F., Biase, I. D., Nezi, L., Ruggiero, G., Tatangelo, F., Pisano, C., Monticelli, A., Garbi, C., Acquaviva, A. M., & Cocozza, S. (2005) · Journal of Cell Science · doi:10.1242/jcs.02516 · Cited by 61 · see citing works
The Cell's Cookbook For Iron–Sulfur Clusters: Recipes For Fool's Gold?
Balk, J., & Lill, R. (2004) · ChemBioChem · doi:10.1002/cbic.200400061 · Cited by 57 · see citing works
Self-citationNakai, Y., Yoshihara, Y., Hayashi, H., & Kagamiyama, H. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00897-7 · Cited by 54 · see citing works
Self-citationBouton, C., Chauveau, M.-J., Lazereg, S., & Drapier, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203276200 · Cited by 44 · see citing works
Elsässer, H. P., Lehr, U., Agricola, B., & Kern, H. F. (1993) · Virchows Archiv B Cell Pathology Including Molecular Pathology · doi:10.1007/bf02915113 · Cited by 40 · see citing works
Deletion of mtDNA disrupts mitochondrial function and structure, but not biogenesis
Holmuhamedov, E. (2003) · Mitochondrion · doi:10.1016/s1567-7249(03)00053-9 · Cited by 36 · see citing works
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Sheftel, A. D., Stehling, O., Pierik, A. J., Elsässer, H.-P., Mühlenhoff, U., Webert, H., Hobler, A., Hannemann, F., Bernhardt, R., & Lill, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004250107 · Cited by 406 · see citing works
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Self-citationStehling, O., & Lill, R. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a011312 · Cited by 228 · see citing works
Self-citationMaio, N., & Rouault, T. A. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.09.009 · Cited by 215 · see citing works
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Self-citationSingh, N., Haldar, S., Tripathi, A. K., Horback, K., Wong, J., Sharma, D., Beserra, A., Suda, S., Anbalagan, C., Dev, S., et al. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4931 · Cited by 205 · see citing works
Iron–sulfur proteins in health and disease
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Gispert, S., Parganlija, D., Klinkenberg, M., Dröse, S., Wittig, I., Mittelbronn, M. G. A., Grzmil, P., Koob, S., Hamann, A., Walter, M. J., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt338 · Cited by 188 · see citing works
Lill, R., Dutkiewicz, R., Freibert, S., Heidenreich, T., Mascarenhas, J., Netz, D. J. A., Paul, V. D., Pierik, A. J., Richter, N., Stümpfig, M., et al. (2015) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2015.05.002 · Cited by 188 · see citing works
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Self-citationStehling, O., Mascarenhas, J., Vashisht, A. A., Sheftel, A. D., Niggemeyer, B., Rösser, R., Pierik, A. J., Wohlschlegel, J. A., & Lill, R. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.06.015 · Cited by 170 · see citing works
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Self-citationShi, Y., Ghosh, M. C., Tong, W.-H., & Rouault, T. A. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp239 · Cited by 155 · see citing works
Cavadini, P., Biasiotto, G., Poli, M., Levi, S., Verardi, R., Zanella, I., Derosas, M., Ingrassia, R., Corrado, M., & Arosio, P. (2006) · Blood · doi:10.1182/blood-2006-08-041632 · Cited by 155 · see citing works
Martelli, A., & Puccio, H. M. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00130 · Cited by 148 · see citing works
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Patel, S. J., Frey, A. G., Palenchar, D. J., Achar, S. R., Zumbrennen‐Bullough, K. B., Vashisht, A. A., Wohlschlegel, J. A., & Philpott, C. C. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0330-6 · Cited by 147 · see citing works
Role of Nfu1 and Bol3 in iron-sulfur cluster transfer to mitochondrial clients
Melber, A., Na, U., Vashisht, A. A., Weiler, B. D., Lill, R., Wohlschlegel, J. A., & Winge, D. R. (2016) · eLife · doi:10.7554/elife.15991 · Cited by 135 · see citing works
Self-citationA Novel Role for Human Nfs1 in the Cytoplasm
Marelja, Z., Stöcklein, W., Nimtz, M., & Leimkühler, S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804064200 · Cited by 134 · see citing works
Frataxin is essential for extramitochondrial Fe–S cluster proteins in mammalian tissues
Martelli, A., Wattenhofer‐Donzé, M., Schmucker, S., Bouvet, S., Reutenauer, L., & Puccio, H. M. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm163 · Cited by 133 · see citing works
Lee, J., You, J. H., Shin, D., & Roh, J. (2020) · Theranostics · doi:10.7150/thno.46903 · Cited by 127 · see citing works
Ferecatu, I., Gonçalves, S., Golinelli‐Cohen, M., Clémancey, M., Martelli, A., Riquier, S., Guittet, É., Latour, J., Puccio, H. M., Drapier, J., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.548438 · Cited by 125 · see citing works
Mutation of the iron-sulfur cluster assembly gene IBA57 causes severe myopathy and encephalopathy
Bolar, N. A., Vanlander, A. V., Wilbrecht, C., der Aa, N. V., Smet, J., Paepe, B. D., Vandeweyer, G., Kooy, R. F., Eyskens, F. J. M., Latter, E. D., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt107 · Cited by 120 · see citing works
Self-citationProtein networks in the maturation of human iron–sulfur proteins
Ciofi‐Baffoni, S., Nasta, V., & Banci, L. (2017) · Metallomics · doi:10.1039/c7mt00269f · Cited by 116 · see citing works
Cellular and mitochondrial remodeling upon defects in iron-sulfur protein biogenesis
Hausmann, A., Samans, B., Lill, R., & Mühlenhoff, U. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m705570200 · Cited by 111 · see citing works
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Haunhorst, P., Hanschmann, E.-M., Bräutigam, L., Stehling, O., Hoffmann, B., Mühlenhoff, U., Lill, R., Berndt, C., & Lillig, C. H. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e12-09-0648 · Cited by 111 · see citing works
Self-citationHidese, R., Mihara, H., & Esaki, N. (2011) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-011-3336-x · Cited by 108 · see citing works
Mammalian Fe–S cluster biogenesis and its implication in disease
Beilschmidt, L. K., & Puccio, H. M. (2014) · Biochimie · doi:10.1016/j.biochi.2014.01.009 · Cited by 107 · see citing works
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Stehling, O., Netz, D. J. A., Niggemeyer, B., Rösser, R., Eisenstein, R. S., Puccio, H. M., Pierik, A. J., & Lill, R. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00545-08 · Cited by 107 · see citing works
Self-citationFujihara, K. M., Zhang, B. Z., Jackson, T. D., Ogunkola, M. O., Nijagal, B., Milne, J. V., Sallman, D. A., Ang, C.-S., Nikolic, I., Kearney, C. J., et al. (2022) · Science Advances · doi:10.1126/sciadv.abm9427 · Cited by 103 · see citing works
“NFS1 har-vests sulfur from cysteine for the biogenesis of ISCs ( 27 ), which are important cofactors for at least 48 enzymes required to support several cell essential functions, including DNA synthesis and mitochondrial respiration (electron transport chain and tricarboxylic acid cycle) (Fig.”
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Xu, X. M., & Møller, S. G. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3259 · Cited by 102 · see citing works
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Mühlenhoff, U., Hoffmann, B., Richter, N., Rietzschel, N., Spantgar, F., Stehling, O., Uzarska, M. A., & Lill, R. (2015) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2015.05.003 · Cited by 95 · see citing works
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Pierik, A. J., Netz, D. J. A., & Lill, R. (2009) · Nature Protocols · doi:10.1038/nprot.2009.39 · Cited by 94 · see citing works
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Freibert, S., Weiler, B. D., Bill, E., Pierik, A. J., Mühlenhoff, U., & Lill, R. (2018) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2017.11.034 · Cited by 92 · see citing works
Self-citationUhrigshardt, H., Singh, A., Kovtunovych, G., Ghosh, M. C., & Rouault, T. A. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq301 · Cited by 91 · see citing works
Frey, A. G., Palenchar, D. J., Wildemann, J. D., & Philpott, C. C. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.744946 · Cited by 86 · see citing works
Lee, D. W., Kaur, D., Chinta, S. J., Rajagopalan, S., & Andersen, J. K. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2489 · Cited by 81 · see citing works
Srinivasan, V., Netz, D. J. A., Webert, H., Mascarenhas, J., Pierik, A. J., Michel, H., & Lill, R. (2007) · Structure · doi:10.1016/j.str.2007.08.009 · Cited by 79 · see citing works
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Feichtinger, R. G., Zimmermann, F., Mayr, J. A., Neureiter, D., Hauser‐Kronberger, C., Schilling, F. H., Jones, N., Sperl, W., & Kofler, B. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-149 · Cited by 78 · see citing works
Nývltová, E., Šuťák, R., Harant, K., Šedinová, M., Hrdý, I., Pačes, J., Vlček, Č., & Tachezy, J. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219590110 · Cited by 77 · see citing works
Farhan, S. M. K., Wang, J., Robinson, J. F., Lahiry, P., Siu, V. M., Prasad, C., Kronick, J. B., Ramsay, D. A., Rupar, C. A., & Hegele, R. A. (2014) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.46 · Cited by 76 · see citing works
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Song, D., & Lee, F. S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708077200 · Cited by 76 · see citing works
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Lill, R. (2020) · Biological Chemistry · doi:10.1515/hsz-2020-0117 · Cited by 75 · see citing works
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Patil, V. A., Fox, J. L., Gohil, V. M., Winge, D. R., & Greenberg, M. L. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.428938 · Cited by 74 · see citing works
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Tobe, R., & Mihara, H. (2018) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2018.05.023 · Cited by 74 · see citing works
Paul, V. D., Mühlenhoff, U., Stümpfig, M., Seebacher, J., Kugler, K., Renicke, C. C., Taxis, C., Gavin, A., Pierik, A. J., & Lill, R. (2015) · eLife · doi:10.7554/elife.08231 · Cited by 72 · see citing works
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Wang, J., Fillebeen, C., Chen, G., Biederbick, A., Lill, R., & Pantopoulos, K. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01111-06 · Cited by 72 · see citing works
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Cardenas‐Rodriguez, M., Chatzi, A., & Tokatlidis, K. (2018) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-018-1548-6 · Cited by 72 · see citing works
ISCA2 inhibition decreases HIF and induces ferroptosis in clear cell renal carcinoma
Green, Y. S., Ferreira dos Santos, M. C., Fuja, D. G., Reichert, E. C., Campos, A. R., Cowman, S. J., Acuña Pilarte, K., Kohan, J., Tripp, S. R., Leibold, E. A., et al. (2022) · Oncogene · doi:10.1038/s41388-022-02460-1 · Cited by 69 · see citing works
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Nakai, Y., Nakai, M., Lill, R., Suzuki, T., & Hayashi, H. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01321-06 · Cited by 66 · see citing works
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Bych, K., Netz, D. J. A., Vigani, G., Bill, E., Lill, R., Pierik, A. J., & Balk, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m807303200 · Cited by 65 · see citing works
Self-citationZanella, I., Derosas, M., Corrado, M., Cocco, E., Cavadini, P., Biasiotto, G., Poli, M., Verardi, R., & Arosio, P. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2007.11.006 · Cited by 60 · see citing works
Iron-sulfur clusters in mitochondrial metabolism: Multifaceted roles of a simple cofactor
Stiban, J., So, M., & Kaguni, L. S. (2016) · Biochemistry (Moscow) · doi:10.1134/s0006297916100059 · Cited by 59 · see citing works
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Nakai, Y., & Maruyama, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103470 · Cited by 57 · see citing works
Self-citationSong, D., Tu, Z., & Lee, F. S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.040014 · Cited by 54 · see citing works
Requirements of the cytosolic iron–sulfur cluster assembly pathway in Arabidopsis
Bernard, D. G., Netz, D. J. A., Lagny, T. J., Pierik, A. J., & Balk, J. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2012.0259 · Cited by 54 · see citing works
Marelja, Z., Chowdhury, M. M., Dosche, C., Hille, C., Baumann, O., Löhmannsröben, H., & Leimkühler, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060869 · Cited by 52 · see citing works
Entamoeba histolytica under Oxidative Stress: What Countermeasure Mechanisms Are in Place?
Pineda, E., & Perdomo, D. (2017) · Cells · doi:10.3390/cells6040044 · Cited by 52 · see citing works
Huang, J., Chen, S., Li, H., Niu, H., Sun, Q., Li, W., Guoqian, T., Li, J., Jin, L., Lyu, J., et al. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.06.011 · Cited by 49 · see citing works
Sheftel, A. D., & Lill, R. (2008) · Annals of Medicine · doi:10.1080/07853890802322229 · Cited by 48 · see citing works
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Shan, Y., & Cortopassi, G. A. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr582 · Cited by 47 · see citing works
The functions of NifS-like proteins in plant sulfur and selenium metabolism
Hoewyk, D. V., Pilon, M., & Pilon‐Smits, E. A. H. (2007) · Plant Science · doi:10.1016/j.plantsci.2007.10.004 · Cited by 46 · see citing works
Synthesis, delivery and regulation of eukaryotic heme and Fe–S cluster cofactors
Barupala, D., Dzul, S. P., Riggs-Gelasco, P. J., & Stemmler, T. L. (2016) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2016.01.010 · Cited by 46 · see citing works
Paul, B. T., Tesfay, L., Winkler, C. R., Torti, F. M., & Torti, S. V. (2019) · Scientific Reports · doi:10.1038/s41598-019-55907-z · Cited by 45 · see citing works
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Saha, P. P., Srivastava, S., Kumar, S. K. P., Sinha, D., & D’Silva, P. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.678508 · Cited by 44 · see citing works
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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Freibert, S., Boniecki, M. T., Stümpfig, C., Schulz, V., Krapoth, N. C., Winge, D. R., Mühlenhoff, U., Stehling, O., Cygler, M., & Lill, R. (2021) · Nature Communications · doi:10.1038/s41467-021-27122-w · Cited by 43 · see citing works
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Sheftel, A. D., Richardson, D. R., Prchal, J. T., & Ponka, P. (2009) · Acta Haematologica · doi:10.1159/000243796 · Cited by 41 · see citing works
Sulfur sequestration promotes multicellularity during nutrient limitation
Kelly, B. L., Carrizo, G., Edwards-Hicks, J., Sanin, D. E., Stanczak, M. A., Priesnitz, C., Flachsmann, L. J., Curtis, J. D., Mittler, G., Musa, Y., et al. (2021) · Nature · doi:10.1038/s41586-021-03270-3 · Cited by 39 · see citing works
Iron–Sulphur Clusters, Their Biosynthesis, and Biological Functions in Protozoan Parasites
Ali, V., & Nozaki, T. (2013) · Advances in Parasitology/Advances in parasitology · doi:10.1016/b978-0-12-407705-8.00001-x · Cited by 39 · see citing works
Sulfur Administration in Fe–S Cluster Homeostasis
Rydz, L., Wróbel, M., & Jurkowska, H. (2021) · Antioxidants · doi:10.3390/antiox10111738 · Cited by 38 · see citing works
Johnson, N. B., Deck, K. M., Nizzi, C. P., & Eisenstein, R. S. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.785741 · Cited by 38 · see citing works
Saha, P. P., Kumar, S. K. P., Srivastava, S., Sinha, D., Pareek, G., & D’Silva, P. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.526665 · Cited by 37 · see citing works
Shared function and moonlighting proteins in molybdenum cofactor biosynthesis
Leimkühler, S. (2017) · Biological Chemistry · doi:10.1515/hsz-2017-0110 · Cited by 37 · see citing works
Mitochondria Export Sulfur Species Required for Cytosolic tRNA Thiolation
Pandey, A., Pain, J., Dziuba, N., Pandey, A. K., Dancis, A., Lindahl, P. A., & Pain, D. (2018) · Cell chemical biology · doi:10.1016/j.chembiol.2018.04.002 · Cited by 35 · see citing works
Fe-S Cluster Biogenesis in Isolated Mammalian Mitochondria
Pandey, A., Pain, J., Ghosh, A., Dancis, A., & Pain, D. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.610402 · Cited by 35 · see citing works
A novel de novo dominant mutation in ISCU associated with mitochondrial myopathy
Legati, A., Reyes, A., Berti, C. C., Stehling, O., Marchet, S., Lamperti, C., Ferrari, A., Robinson, A. J., Mühlenhoff, U., Lill, R., et al. (2017) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2017-104822 · Cited by 33 · see citing works
Self-citationFe/S protein biogenesis in trypanosomes — A review
Lukeš, J., & Basu, S. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.08.015 · Cited by 31 · see citing works
Fe–S Cluster Assembly in Oxymonads and Related Protists
Vacek, V., Novák, L., Treitli, S. C., Táborský, P., Čepička, I., Kolísko, M., Keeling, P. J., & Hampl, V. (2018) · Molecular Biology and Evolution · doi:10.1093/molbev/msy168 · Cited by 31 · see citing works
Inborn errors of metabolism associated with 3-methylglutaconic aciduria
Jones, D. E., Klacking, E. E., & Ryan, R. O. (2021) · Clinica Chimica Acta · doi:10.1016/j.cca.2021.08.016 · Cited by 29 · see citing works
Nakai, Y., Nakai, M., & Yano, T. (2017) · Biomolecules · doi:10.3390/biom7010017 · Cited by 29 · see citing works
Self-citation
- 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
- 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
- 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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