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Gene Review

ISU1  -  iron-binding protein ISU1

Saccharomyces cerevisiae S288c

Synonyms: Iron sulfur cluster assembly protein 1, mitochondrial, Iron sulfur cluster scaffold protein 1, NUA1, YPL135W
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Disease relevance of ISU1


High impact information on ISU1

  • The mitochondrial proteins Isu1p and Isu2p play an essential role in the maturation of cellular iron-sulfur (Fe/S) proteins in eukaryotes [2].
  • In contrast, depletion of the Hsp70 chaperone Ssq1p, its co-chaperone Jac1p or the glutaredoxin Grx5p markedly increased the amount of Fe/S clusters bound to Isu1p, even though these mitochondrial proteins are crucial for maturation of Fe/S proteins [2].
  • We suggest that NFU1 and ISU1 gene products play a role in iron homeostasis, perhaps in assembly, insertion, and/or repair of mitochondrial Fe-S clusters [3].
  • Quantitative RT-PCR studies confirmed the significant down-regulation of Isu1, CPOX and ferrochelatase at 10 weeks in mouse hearts [4].
  • We were unable to mislocalize Isu1p to the cytosol due to the presence of multiple, independent mitochondrial targeting signals in this protein [5].

Biological context of ISU1

  • FRR3 was found to be homologous to ISU1 and ISU2 of S. cerevisiae, which form mitochondrial iron-sulfur complexes; FRR4 was found to be homologous to YFH1, the yeast frataxin homologue, which also participates in iron-sulfur cluster biogenesis [6].
  • Finally, we have demonstrated through cross-linking studies that ferredoxin, an electron-transport protein, forms a complex with ISU1 in both apo and holo states [7].
  • 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 [8].

Anatomical context of ISU1


Associations of ISU1 with chemical compounds

  • Using a spectroscopic assay, we have analyzed the potential role of the chaperones in Fe/S cluster assembly on the scaffold protein Isu1p in vitro in the presence of the cysteine desulfurase Nfs1p [8].
  • Here, we show that a marked change in the electrostatic properties of a specific region of Yfh1 surface-by substituting two or four acidic residues by lysine or alanine, respectively-impairs Fe-S cluster assembly, weakens the interaction between Yfh1 and Isu1, and increases oxidative damage [9].

Physical interactions of ISU1

  • Consistent with this idea, these Isu1p mutants were capable of binding an Fe/S cluster in vivo but failed to restore the growth and Fe/S cluster assembly defects of a Isu1p/Isu2p-deficient yeast strain [8].

Other interactions of ISU1

  • They have been designated ISU1 and ISU2 [3].
  • Characterization of the interaction between the J-protein Jac1p and the scaffold for Fe-S cluster biogenesis, Isu1p [10].
  • Taken together, these data suggest that Ssq1p/Jac1p/Mge1p are not important for Fe/S cluster synthesis on Isu1p [8].

Analytical, diagnostic and therapeutic context of ISU1

  • UV-vis absorption and Mössbauer spectroscopies (delta = 0.29 +/- 0.05 mm/s; DeltaE(Q) = 0.59 +/- 0.05 mm/s) were used to characterize D37A ISU1 and show the presence of [2Fe-2S](2+) clusters in each subunit [7].


  1. Saccharomyces cerevisiae ISU1 and ISU2: members of a well-conserved gene family for iron-sulfur cluster assembly. Garland, S.A., Hoff, K., Vickery, L.E., Culotta, V.C. J. Mol. Biol. (1999) [Pubmed]
  2. Components involved in assembly and dislocation of iron-sulfur clusters on the scaffold protein Isu1p. Mühlenhoff, U., Gerber, J., Richhardt, N., Lill, R. EMBO J. (2003) [Pubmed]
  3. Evidence for a conserved system for iron metabolism in the mitochondria of Saccharomyces cerevisiae. Schilke, B., Voisine, C., Beinert, H., Craig, E. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  4. Frataxin deficiency alters heme pathway transcripts and decreases mitochondrial heme metabolites in mammalian cells. Schoenfeld, R.A., Napoli, E., Wong, A., Zhan, S., Reutenauer, L., Morin, D., Buckpitt, A.R., Taroni, F., Lonnerdal, B., Ristow, M., Puccio, H., Cortopassi, G.A. Hum. Mol. Genet. (2005) [Pubmed]
  5. The yeast scaffold proteins Isu1p and Isu2p are required inside mitochondria for maturation of cytosolic Fe/S proteins. Gerber, J., Neumann, K., Prohl, C., Mühlenhoff, U., Lill, R. Mol. Cell. Biol. (2004) [Pubmed]
  6. Mitochondrial functioning of constitutive iron uptake mutations in Cryptococcus neoformans. Jacobson, E.S., Troy, A.J., Nyhus, K.J. Mycopathologia (2005) [Pubmed]
  7. Characterization of an iron-sulfur cluster assembly protein (ISU1) from Schizosaccharomyces pombe. Wu, G., Mansy, S.S., Wu Sp, S.P., Surerus, K.K., Foster, M.W., Cowan, J.A. Biochemistry (2002) [Pubmed]
  8. 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]
  9. Acidic residues of yeast frataxin have an essential role in Fe-S cluster assembly. Foury, F., Pastore, A., Trincal, M. EMBO Rep. (2007) [Pubmed]
  10. Characterization of the interaction between the J-protein Jac1p and the scaffold for Fe-S cluster biogenesis, Isu1p. Andrew, A.J., Dutkiewicz, R., Knieszner, H., Craig, E.A., Marszalek, J. J. Biol. Chem. (2006) [Pubmed]
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