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Gene Review

NFS1  -  Nfs1p

Saccharomyces cerevisiae S288c

Synonyms: Cysteine desulfurase, mitochondrial, SPL1, YCL017C, YCL17C, tRNA-splicing protein SPL1
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High impact information on NFS1

  • We show that Isd11 forms a stable complex with Nfs1, the cysteine desulfurase of the mitochondrial machinery for Fe/S cluster assembly [1].
  • We propose that Isd11 acts together with Nfs1 in an early step in the biogenesis of Fe/S proteins [1].
  • The ATP-binding cassette (ABC) transporter Atm1p of the mitochondrial inner membrane performs an essential function only in the generation of cytosolic Fe/S proteins by mediating export of Fe/S cluster precursors synthesized by Nfs1p and other mitochondrial proteins [2].
  • In the absence of chaperones, the kinetics of Fe/S cluster formation on Isu1p were compatible with a chemical reconstitution pathway with Nfs1p functioning as a sulfide donor [3].
  • However, this stimulatory effect of Ssq1p required neither ATP nor Jac1p and could be fully attributed to the activation of the Nfs1p desulfurase activity by Ssq1p [3].

Biological context of NFS1

  • When this sequence was mutated to RRGSR, the mutant protein could not restore cell growth under chromosomal NFS1-depleted conditions [4].
  • The third suppressor gene identified was NFS1 [5].
  • The mutation mapped on chromosome III to an essential 1.5-kb open reading frame (L. S. Symington and T. D. Petes, Mol. Cell. Biol. 8:595-604, 1988), recently named NFS1 (S. G. Oliver et al., Nature [London] 357:38-46, 1992), located adjacent (centromere proximal) to LEU2 [6].
  • Cysteine is utilized by the cysteine desulfurase Nfs1p to release sulfan sulfur; ATP presumably reflects the function of the Hsp70 family chaperone Ssq1p; and NADH is used for reduction of the ferredoxin Yah1p involved in Fe/S protein biogenesis [7].
  • The results demonstrate that Nfs1 protein is required for the proper post-translational modification of the lipoamide-containing mitochondrial subproteome in yeast and pave the road toward a thorough understanding of its precise role in lipoic acid synthesis [8].

Anatomical context of NFS1

  • When AUG1 of the yeast NFS1 gene was mutated to UUG and the resulting mRNA was translated in vitro using a reticulocyte system, initiation from the mutated codon was abolished and occurred instead at downstream codons at increased rates [9].
  • The Nfs1 interacting protein Isd11 has an essential role in Fe/S cluster biogenesis in mitochondria [1].
  • Nfs1p could not assemble an Fe/S cluster on the Isu scaffold proteins when they were located in the yeast cytosol [10].

Associations of NFS1 with chemical compounds

  • In addition, upstream of the PaLEU2 the 3'-terminal half of a gene of the same orientation, encoding a homologue of the S. cerevisiae NFS1/SPL1 gene that encodes a mitochondrial cysteine desulphurase involved in both tRNA processing and mitochondrial metabolism, was found [11].
  • 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 [12].
  • Mass spectrometry analysis revealed an increase in 5-methoxycarbonylmethyluridine concomitant with a decrease in mcm(5)s(2)U in cy-tRNAs that were prepared from Nfs1p-depleted cells [13].

Other interactions of NFS1

  • Taken together these results suggest a role for Ssq1p, Jac1p, and Nfs1p in assembly/maturation of mitochondrial iron-sulfur proteins and that one or more of the target Fe/S proteins contribute to oxidative damage in cells lacking copper/zinc SOD [5].

Analytical, diagnostic and therapeutic context of NFS1

  • Comparison and identification of mitochondrial matrix proteins from wild-type and cysteine desulfurase-defective (nfs1-14, carrying a hypomorphic allele of NFS1) yeast strains, using two-dimensional gel electrophoresis coupled to mass spectrometry analyses, revealed large changes in the amounts of various proteins [8].


  1. The 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. EMBO J. (2006) [Pubmed]
  2. The mitochondrial proteins Atm1p and Nfs1p are essential for biogenesis of cytosolic Fe/S proteins. Kispal, G., Csere, P., Prohl, C., Lill, R. EMBO J. (1999) [Pubmed]
  3. The Hsp70 chaperone Ssq1p is dispensable for iron-sulfur cluster formation on the scaffold protein Isu1p. Dutkiewicz, R., Marszalek, J., Schilke, B., Craig, E.A., Lill, R., Mühlenhoff, U. J. Biol. Chem. (2006) [Pubmed]
  4. Nuclear localization of yeast Nfs1p is required for cell survival. Nakai, Y., Nakai, M., Hayashi, H., Kagamiyama, H. J. Biol. Chem. (2001) [Pubmed]
  5. Suppressors of superoxide dismutase (SOD1) deficiency in Saccharomyces cerevisiae. Identification of proteins predicted to mediate iron-sulfur cluster assembly. Strain, J., Lorenz, C.R., Bode, J., Garland, S., Smolen, G.A., Ta, D.T., Vickery, L.E., Culotta, V.C. J. Biol. Chem. (1998) [Pubmed]
  6. SPL1-1, a Saccharomyces cerevisiae mutation affecting tRNA splicing. Kolman, C., Söll, D. J. Bacteriol. (1993) [Pubmed]
  7. Characterization of iron-sulfur protein assembly in isolated mitochondria. A requirement for ATP, NADH, and reduced iron. Mühlenhoff, U., Richhardt, N., Gerber, J., Lill, R. J. Biol. Chem. (2002) [Pubmed]
  8. Modifications of the lipoamide-containing mitochondrial subproteome in a yeast mutant defective in cysteine desulfurase. Onder, O., Yoon, H., Naumann, B., Hippler, M., Dancis, A., Daldal, F. Mol. Cell Proteomics (2006) [Pubmed]
  9. The AUG start codon of the Saccharomyces cerevisiae NFS1 gene can be substituted for by UUG without increased initiation of translation at downstream codons. Nett, J.H., Kessl, J., Wenz, T., Trumpower, B.L. Eur. J. Biochem. (2001) [Pubmed]
  10. Functional characterization of the eukaryotic cysteine desulfurase Nfs1p from Saccharomyces cerevisiae. Mühlenhoff, U., Balk, J., Richhardt, N., Kaiser, J.T., Sipos, K., Kispal, G., Lill, R. J. Biol. Chem. (2004) [Pubmed]
  11. Cloning and sequence analysis of the LEU2 homologue gene from Pichia anomala. De la Rosa, J.M., Pérez, J.A., Gutiérrez, F., González, J.M., Ruiz, T., Rodríguez, L. Yeast (2001) [Pubmed]
  12. Yeast mitochondrial protein, Nfs1p, coordinately regulates iron-sulfur cluster proteins, cellular iron uptake, and iron distribution. Li, J., Kogan, M., Knight, S.A., Pain, D., Dancis, A. J. Biol. Chem. (1999) [Pubmed]
  13. 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. J. Biol. Chem. (2004) [Pubmed]
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