Previous Article | Next Article 
Molecular and Cellular Biology, June 2004, p. 4848-4857, Vol. 24, No. 11
0270-7306/04/$08.00+0 DOI: 10.1128/MCB.24.11.4848-4857.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
The Yeast Scaffold Proteins Isu1p and Isu2p Are Required inside Mitochondria for Maturation of Cytosolic Fe/S Proteins
Jana Gerber, Karina Neumann, Corinna Prohl, Ulrich Mühlenhoff, and Roland Lill*
Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, D-35033 Marburg, Germany
Received 23 October 2003/
Returned for modification 29 December 2003/
Accepted 8 March 2004
Iron-sulfur (Fe/S) proteins are located in mitochondria, cytosol, and nucleus. Mitochondrial Fe/S proteins are matured by the iron-sulfur cluster (ISC) assembly machinery. Little is known about the formation of Fe/S proteins in the cytosol and nucleus. A function of mitochondria in cytosolic Fe/S protein maturation has been noted, but small amounts of some ISC components have been detected outside mitochondria. Here, we studied the highly conserved yeast proteins Isu1p and Isu2p, which provide a scaffold for Fe/S cluster synthesis. We asked whether the Isu proteins are needed for biosynthesis of cytosolic Fe/S clusters and in which subcellular compartment the Isu proteins are required. The Isu proteins were found to be essential for de novo biosynthesis of both mitochondrial and cytosolic Fe/S proteins. Several lines of evidence indicate that Isu1p and Isu2p have to be located inside mitochondria in order to perform their function in cytosolic Fe/S protein maturation. We were unable to mislocalize Isu1p to the cytosol due to the presence of multiple, independent mitochondrial targeting signals in this protein. Further, the bacterial homologue IscU and the human Isu proteins (partially) complemented the defects of yeast Isu protein-depleted cells in growth rate, Fe/S protein biogenesis, and iron homeostasis, yet only after targeting to mitochondria. Together, our data suggest that the Isu proteins need to be localized in mitochondria to fulfill their functional requirement in Fe/S protein maturation in the cytosol.
* Corresponding author. Mailing address: Institut für Zytobiologie und Zytopathologie, Philipps-Universität Marburg, Robert-Koch Strasse 6, D-35033 Marburg, Germany. Phone: 49-6421-286 6449. Fax: 49-6421-286 6414. E-mail:
Lill{at}mailer.uni-marburg.de.
Molecular and Cellular Biology, June 2004, p. 4848-4857, Vol. 24, No. 11
0022-538X/04/$08.00+0 DOI: 10.1128/MCB.24.11.4848-4857.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Naranuntarat, A., Jensen, L. T., Pazicni, S., Penner-Hahn, J. E., Culotta, V. C.
(2009). The Interaction of Mitochondrial Iron with Manganese Superoxide Dismutase. J. Biol. Chem.
284: 22633-22640
[Abstract]
[Full Text]
-
Li, H., Gakh, O., Smith, D. Y. IV, Isaya, G.
(2009). Oligomeric Yeast Frataxin Drives Assembly of Core Machinery for Mitochondrial Iron-Sulfur Cluster Synthesis. J. Biol. Chem.
284: 21971-21980
[Abstract]
[Full Text]
-
Andrew, A. J., Song, J.-Y., Schilke, B., Craig, E. A.
(2008). Posttranslational Regulation of the Scaffold for Fe-S Cluster Biogenesis, Isu. Mol. Biol. Cell
19: 5259-5266
[Abstract]
[Full Text]
-
Huang, B., Lu, J., Bystrom, A. S.
(2008). A genome-wide screen identifies genes required for formation of the wobble nucleoside 5-methoxycarbonylmethyl-2-thiouridine in Saccharomyces cerevisiae. RNA
14: 2183-2194
[Abstract]
[Full Text]
-
Stehling, O., Netz, D. J. A., Niggemeyer, B., Rosser, R., Eisenstein, R. S., Puccio, H., Pierik, A. J., Lill, R.
(2008). Human Nbp35 Is Essential for both Cytosolic Iron-Sulfur Protein Assembly and Iron Homeostasis. Mol. Cell. Biol.
28: 5517-5528
[Abstract]
[Full Text]
-
Gelling, C., Dawes, I. W., Richhardt, N., Lill, R., Muhlenhoff, U.
(2008). Mitochondrial Iba57p Is Required for Fe/S Cluster Formation on Aconitase and Activation of Radical SAM Enzymes. Mol. Cell. Biol.
28: 1851-1861
[Abstract]
[Full Text]
-
Dolezal, P., Dancis, A., Lesuisse, E., Sutak, R., Hrdy, I., Embley, T. M., Tachezy, J.
(2007). Frataxin, a Conserved Mitochondrial Protein, in the Hydrogenosome of Trichomonas vaginalis. Eukaryot Cell
6: 1431-1438
[Abstract]
[Full Text]
-
Nakai, Y., Nakai, M., Lill, R., Suzuki, T., Hayashi, H.
(2007). Thio Modification of Yeast Cytosolic tRNA Is an Iron-Sulfur Protein-Dependent Pathway. Mol. Cell. Biol.
27: 2841-2847
[Abstract]
[Full Text]
-
Muhlenhoff, U., Gerl, M. J., Flauger, B., Pirner, H. M., Balser, S., Richhardt, N., Lill, R., Stolz, J.
(2007). The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae. Eukaryot Cell
6: 495-504
[Abstract]
[Full Text]
-
Burri, L., Williams, B. A. P., Bursac, D., Lithgow, T., Keeling, P. J.
(2006). Microsporidian mitosomes retain elements of the general mitochondrial targeting system. Proc. Natl. Acad. Sci. USA
103: 15916-15920
[Abstract]
[Full Text]
-
Rise, M. L, Douglas, S. E, Sakhrani, D., Williams, J., Ewart, K V., Rise, M., Davidson, W. S, Koop, B. F, Devlin, R. H
(2006). Multiple microarray platforms utilized for hepatic gene expression profiling of GH transgenic coho salmon with and without ration restriction.. J Mol Endocrinol
37: 259-282
[Abstract]
[Full Text]
-
Biederbick, A., Stehling, O., Rosser, R., Niggemeyer, B., Nakai, Y., Elsasser, H.-P., Lill, R.
(2006). Role of Human Mitochondrial Nfs1 in Cytosolic Iron-Sulfur Protein Biogenesis and Iron Regulation. Mol. Cell. Biol.
26: 5675-5687
[Abstract]
[Full Text]
-
Dutkiewicz, R., Marszalek, J., Schilke, B., Craig, E. A., Lill, R., Muhlenhoff, U.
(2006). The Hsp70 Chaperone Ssq1p Is Dispensable for Iron-Sulfur Cluster Formation on the Scaffold Protein Isu1p. J. Biol. Chem.
281: 7801-7808
[Abstract]
[Full Text]
-
Hausmann, A., Aguilar Netz, D. J., Balk, J., Pierik, A. J., Muhlenhoff, U., Lill, R.
(2005). The eukaryotic P loop NTPase Nbp35: An essential component of the cytosolic and nuclear iron-sulfur protein assembly machinery. Proc. Natl. Acad. Sci. USA
102: 3266-3271
[Abstract]
[Full Text]
-
Lesuisse, E., Knight, S. A. B., Courel, M., Santos, R., Camadro, J.-M., Dancis, A.
(2005). Genome-Wide Screen for Genes With Effects on Distinct Iron Uptake Activities in Saccharomyces cerevisiae. Genetics
169: 107-122
[Abstract]
[Full Text]
-
Molina, M. M., Belli, G., de la Torre, M. A., Rodriguez-Manzaneque, M. T., Herrero, E.
(2004). Nuclear Monothiol Glutaredoxins of Saccharomyces cerevisiae Can Function as Mitochondrial Glutaredoxins. J. Biol. Chem.
279: 51923-51930
[Abstract]
[Full Text]
-
Muhlenhoff, U., Balk, J., Richhardt, N., Kaiser, J. T., Sipos, K., Kispal, G., Lill, R.
(2004). Functional Characterization of the Eukaryotic Cysteine Desulfurase Nfs1p from Saccharomyces cerevisiae. J. Biol. Chem.
279: 36906-36915
[Abstract]
[Full Text]