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J Biol Chem, Vol. 274, Issue 46, 33025-33034, November 12, 1999
From the Nfs1p is the yeast homolog of the bacterial
proteins NifS and IscS, enzymes that release sulfur from cysteine for
iron-sulfur cluster assembly. Here we show that the yeast mitochondrial
protein Nfs1p regulates cellular and mitochondrial iron homeostasis. A strain of Saccharomyces cerevisiae, MA14, with a missense
NFS1 allele (I191S) was isolated in a screen for altered
iron-dependent gene regulation. This mutant exhibited
constitutive up-regulation of the genes of the cellular iron uptake
system, mediated through effects on the Aft1p iron-regulatory protein.
Iron accumulating in the mutant cells was retained in the mitochondrial
matrix while, at the same time, iron-sulfur proteins were deficient. In
this work, the yeast protein was localized to mitochondria, and the gene was shown to be essential for viability. Furthermore, Nfs1p in the
MA14 mutant was found to be markedly decreased, suggesting that this
low protein level produced the observed regulatory effects. This
hypothesis was confirmed by experiments in which expression of
wild-type Nfs1p from a regulated galactose-induced promoter was
turned off, leading to recapitulation of the iron regulatory phenotypes
characteristic of the MA14 mutant. These phenotypes include decreases
in iron-sulfur protein activities coordinated with increases in
cellular iron uptake and iron distribution to mitochondria.
Yeast Mitochondrial Protein, Nfs1p, Coordinately Regulates
Iron-Sulfur Cluster Proteins, Cellular Iron Uptake, and Iron
Distribution
,,,
Department of Medicine, Division of
Hematology-Oncology, University of Pennsylvania, Philadelphia,
Pennsylvania 19104 and the § Department of Physiology,
University of Pennsylvania School of Medicine,
Philadelphia, Pennsylvania 19104
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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C. J. Schwartz, O. Djaman, J. A. Imlay, and P. J. Kiley The cysteine desulfurase, IscS, has a major role in in vivo Fe-S cluster formation in Escherichia coli PNAS, July 19, 2000; (2000) 160261497. [Abstract] [Full Text]
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K. G. Hoff, J. J. Silberg, and L. E. Vickery Interaction of the iron-sulfur cluster assembly protein IscU with the Hsc66/Hsc20 molecular chaperone system of Escherichiacoli PNAS, June 23, 2000; (2000) 130201997. [Abstract] [Full Text]
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C. T. Lauhon and R. Kambampati The iscS Gene in Escherichia coli Is Required for the Biosynthesis of 4-Thiouridine, Thiamin, and NAD J. Biol. Chem., June 23, 2000; 275(26): 20096 - 20103. [Abstract] [Full Text] [PDF]
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J. Li, S. Saxena, D. Pain, and A. Dancis Adrenodoxin Reductase Homolog (Arh1p) of Yeast Mitochondria Required for Iron Homeostasis J. Biol. Chem., January 5, 2001; 276(2): 1503 - 1509. [Abstract] [Full Text] [PDF]
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Y. Nakai, M. Nakai, H. Hayashi, and H. Kagamiyama Nuclear Localization of Yeast Nfs1p Is Required for Cell Survival J. Biol. Chem., March 9, 2001; 276(11): 8314 - 8320. [Abstract] [Full Text] [PDF]
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R. Kim, S. Saxena, D. M. Gordon, D. Pain, and A. Dancis J-domain Protein, Jac1p, of Yeast Mitochondria Required for Iron Homeostasis and Activity of Fe-S Cluster Proteins J. Biol. Chem., May 11, 2001; 276(20): 17524 - 17532. [Abstract] [Full Text] [PDF]
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A. Kaut, H. Lange, K. Diekert, G. Kispal, and R. Lill Isa1p Is a Component of the Mitochondrial Machinery for Maturation of Cellular Iron-Sulfur Proteins and Requires Conserved Cysteine Residues for Function J. Biol. Chem., May 19, 2000; 275(21): 15955 - 15961. [Abstract] [Full Text] [PDF]
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S.-i. Kato, H. Mihara, T. Kurihara, Y. Takahashi, U. Tokumoto, T. Yoshimura, and N. Esaki Cys-328 of IscS and Cys-63 of IscU are the sites of disulfide bridge formation in a covalently bound IscS/IscU complex: Implications for the mechanism of iron-sulfur cluster assembly PNAS, April 30, 2002; 99(9): 5948 - 5952. [Abstract] [Full Text] [PDF]
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K. G. Hoff, J. J. Silberg, and L. E. Vickery Interaction of the iron-sulfur cluster assembly protein IscU with the Hsc66/Hsc20 molecular chaperone system of Escherichiacoli PNAS, July 5, 2000; 97(14): 7790 - 7795. [Abstract] [Full Text] [PDF]
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C. J. Schwartz, O. Djaman, J. A. Imlay, and P. J. Kiley The cysteine desulfurase, IscS, has a major role in in vivo Fe-S cluster formation in Escherichia coli PNAS, August 1, 2000; 97(16): 9009 - 9014. [Abstract] [Full Text] [PDF]
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M. T. Rodriguez-Manzaneque, J. Tamarit, G. Belli, J. Ros, and E. Herrero Grx5 Is a Mitochondrial Glutaredoxin Required for the Activity of Iron/Sulfur Enzymes Mol. Biol. Cell, April 1, 2002; 13(4): 1109 - 1121. [Abstract] [Full Text] [PDF]
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