ISU1

Summary

Gene Symbol: ISU1
Description: iron-binding protein ISU1
Alias: NUA1, iron-binding protein ISU1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Ciesielski S, Schilke B, Osipiuk J, Bigelow L, Mulligan R, Majewska J, et al. Interaction of J-protein co-chaperone Jac1 with Fe-S scaffold Isu is indispensable in vivo and conserved in evolution. J Mol Biol. 2012;417:1-12 pubmed publisher
    ..However, in apparent contradiction, we previously reported that an 8-fold decrease in Jac1's affinity for Isu1 is well tolerated in vivo, raising the question as to whether the Jac1:Isu interaction actually plays an important ..
  2. Muhlenhoff U, Gerber J, Richhardt N, Lill R. Components involved in assembly and dislocation of iron-sulfur clusters on the scaffold protein Isu1p. EMBO J. 2003;22:4815-25 pubmed
    ..We propose a model that dissects Fe/S cluster biogenesis into two major steps and assigns its central components to one of these two steps. ..
  3. Knieszner H, Schilke B, Dutkiewicz R, D Silva P, Cheng S, Ohlson M, et al. Compensation for a defective interaction of the hsp70 ssq1 with the mitochondrial Fe-S cluster scaffold isu. J Biol Chem. 2005;280:28966-72 pubmed
    ..no detectable affinity for Isu, are indistinguishable from Deltassq1 cells, underscoring the importance of the Ssq1-Isu1 interaction in vivo...
  4. Dutkiewicz R, Marszalek J, Schilke B, Craig E, Lill R, Muhlenhoff U. The Hsp70 chaperone Ssq1p is dispensable for iron-sulfur cluster formation on the scaffold protein Isu1p. J Biol Chem. 2006;281:7801-8 pubmed
    ..Hence, consistent with previous in vivo data, these chaperones likely function in steps subsequent to the de novo synthesis of the Fe/S cluster on Isu1p. ..
  5. Andrew A, Dutkiewicz R, Knieszner H, Craig E, Marszalek J. Characterization of the interaction between the J-protein Jac1p and the scaffold for Fe-S cluster biogenesis, Isu1p. J Biol Chem. 2006;281:14580-7 pubmed
    ..We propose that Isu protein targeting may be particularly important when environmental conditions place high demands on Fe-S cluster biogenesis or in organisms lacking specialized Hsp70s for Fe-S cluster biogenesis. ..
  6. Dutkiewicz R, Schilke B, Cheng S, Knieszner H, Craig E, Marszalek J. Sequence-specific interaction between mitochondrial Fe-S scaffold protein Isu and Hsp70 Ssq1 is essential for their in vivo function. J Biol Chem. 2004;279:29167-74 pubmed
  7. Gerber J, Muhlenhoff U, Lill R. An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1. EMBO Rep. 2003;4:906-11 pubmed
    ..specifically binds to the central Fe/S-cluster (ISC)-assembly complex, which is composed of the scaffold protein Isu1 and the cysteine desulphurase Nfs1...
  8. Uzarska M, Dutkiewicz R, Freibert S, Lill R, Muhlenhoff U. The mitochondrial Hsp70 chaperone Ssq1 facilitates Fe/S cluster transfer from Isu1 to Grx5 by complex formation. Mol Biol Cell. 2013;24:1830-41 pubmed publisher
    ..Similar to its bacterial orthologue HscA, Ssq1 binds to the scaffold protein Isu1, thereby facilitating dissociation of the newly synthesized Fe/S cluster on Isu1 and its transfer to target ..
  9. Ciesielski S, Schilke B, Marszalek J, Craig E. Protection of scaffold protein Isu from degradation by the Lon protease Pim1 as a component of Fe-S cluster biogenesis regulation. Mol Biol Cell. 2016;27:1060-8 pubmed publisher

More Information

Publications38

  1. Li H, Gakh O, Smith D, Isaya G. Oligomeric yeast frataxin drives assembly of core machinery for mitochondrial iron-sulfur cluster synthesis. J Biol Chem. 2009;284:21971-80 pubmed publisher
    ..Moreover, both Yfh1 and Nfs1-Isd11 can directly bind to the scaffold, Isu1. Binding of Yfh1 to Nfs1-Isd11 or Isu1 requires oligomerization of Yfh1 and can occur in an iron-independent manner...
  2. Ramazzotti A, Vanmansart V, Foury F. Mitochondrial functional interactions between frataxin and Isu1p, the iron-sulfur cluster scaffold protein, in Saccharomyces cerevisiae. FEBS Lett. 2004;557:215-20 pubmed
    ..Analysis of the cellular phenotypes resulting from pairwise combinations of yfh1 and isu1 mutations, and cross-linking experiments in isolated mitochondria provide evidence for a direct interaction between ..
  3. Jensen L, Sanchez R, Srinivasan C, Valentine J, Culotta V. Mutations in Saccharomyces cerevisiae iron-sulfur cluster assembly genes and oxidative stress relevant to Cu,Zn superoxide dismutase. J Biol Chem. 2004;279:29938-43 pubmed
    ..By comparison, the sod1Delta lysine auxotrophy appears to be reversed in the seo mutants by increased expression of genes in the lysine biosynthetic pathway, perhaps through sensing of mitochondrial damage by the retrograde response. ..
  4. Yoon H, Golla R, Lesuisse E, Pain J, Donald J, Lyver E, et al. Mutation in the Fe-S scaffold protein Isu bypasses frataxin deletion. Biochem J. 2012;441:473-80 pubmed publisher
    ..we report that a single amino acid substitution (methionine to isoleucine) at position 107 in the mature form of Isu1 restored many deficient functions in ?yfh1 or frataxin-depleted yeast cells...
  5. Cook J, Kondapalli K, Rawat S, Childs W, Murugesan Y, Dancis A, et al. Molecular details of the yeast frataxin-Isu1 interaction during mitochondrial Fe-S cluster assembly. Biochemistry. 2010;49:8756-65 pubmed publisher
    ..have shown frataxin interacts with the iron-sulfur cluster assembly scaffold protein (in yeast, there are two, Isu1 and Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by serving as an iron chaperone in ..
  6. Daniel J. Direct in vivo access to potential gene targets of the RPD3 histone deactylase using fitness-based interferential genetics. Yeast. 2007;24:575-87 pubmed
    ..Finally, the other selected genes, ISU1, involved in the biosynthesis of the iron-sulphur cluster in mitochondria, and the less well functionally defined ..
  7. Yoon H, Knight S, Pandey A, Pain J, Turkarslan S, Pain D, et al. Turning Saccharomyces cerevisiae into a Frataxin-Independent Organism. PLoS Genet. 2015;11:e1005135 pubmed publisher
    ..interacting with other components of the Fe-S cluster machinery, including cysteine desulfurase Nfs1, Isd11 and the Isu1 scaffold protein. Yeast Isu1 with the methionine to isoleucine substitution (M141I), in which the E...
  8. Schilke B, Voisine C, Beinert H, Craig E. Evidence for a conserved system for iron metabolism in the mitochondria of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1999;96:10206-11 pubmed
    ..They have been designated ISU1 and ISU2. Isu1, Isu2, and Nfu1 are located in the mitochondrial matrix...
  9. Foury F, Pastore A, Trincal M. Acidic residues of yeast frataxin have an essential role in Fe-S cluster assembly. EMBO Rep. 2007;8:194-9 pubmed
    ..by lysine or alanine, respectively - impairs Fe-S cluster assembly, weakens the interaction between Yfh1 and Isu1, and increases oxidative damage...
  10. Li L, Kaplan J, Ward D. The glucose sensor Snf1 and the transcription factors Msn2 and Msn4 regulate transcription of the vacuolar iron importer gene CCC1 and iron resistance in yeast. J Biol Chem. 2017;292:15577-15586 pubmed publisher
    ..In conclusion, we show that yeast have developed multiple transcriptional mechanisms to regulate Ccc1 expression and to protect against high cytosolic iron toxicity. ..
  11. Yoon H, Knight S, Pandey A, Pain J, Zhang Y, Pain D, et al. Frataxin-bypassing Isu1: characterization of the bypass activity in cells and mitochondria. Biochem J. 2014;459:71-81 pubmed publisher
    ..In the present study we created strains expressing a single scaffold protein, either Isu1 or the bypass mutant M107I Isu1...
  12. Patil V, Fox J, Gohil V, Winge D, Greenberg M. Loss of cardiolipin leads to perturbation of mitochondrial and cellular iron homeostasis. J Biol Chem. 2013;288:1696-705 pubmed publisher
    ..Consistent with an Fe-S defect, deletion of ISU1, one of two ISU genes that encode the mitochondrial Fe-S scaffolding protein essential for the synthesis of Fe-S ..
  13. Sato T, Tremaine M, Parreiras L, Hebert A, Myers K, Higbee A, et al. Directed Evolution Reveals Unexpected Epistatic Interactions That Alter Metabolic Regulation and Enable Anaerobic Xylose Use by Saccharomyces cerevisiae. PLoS Genet. 2016;12:e1006372 pubmed publisher
    ..Kinase A (PKA) signaling (IRA2), and a scaffolding protein for mitochondrial iron-sulfur (Fe-S) cluster biogenesis (ISU1)...
  14. Naranuntarat A, Jensen L, Pazicni S, Penner Hahn J, Culotta V. The interaction of mitochondrial iron with manganese superoxide dismutase. J Biol Chem. 2009;284:22633-40 pubmed publisher
    ..In all cases where disruptions in iron homeostasis inactivated Sod2p, we observed an increase in mitochondrial Isu proteins. These studies indicate that the Isu proteins and the iron-sulfur pathway can donate iron to Sod2p...
  15. Nakai Y, Nakai M, Lill R, Suzuki T, Hayashi H. Thio modification of yeast cytosolic tRNA is an iron-sulfur protein-dependent pathway. Mol Cell Biol. 2007;27:2841-7 pubmed
    ..Interestingly, the mitochondrial scaffold proteins Isu1 and Isu2 are required for the 2-thio modification of the cy-tRNAs but not of the mt-tRNAs, while mitochondrial Nfs1 ..
  16. Mozolewska M, Krupa P, Scheraga H, Liwo A. Molecular modeling of the binding modes of the iron-sulfur protein to the Jac1 co-chaperone from Saccharomyces cerevisiae by all-atom and coarse-grained approaches. Proteins. 2015;83:1414-26 pubmed publisher
    The iron-sulfur protein 1 (Isu1) and the J-type co-chaperone Jac1 from yeast are part of a huge ATP-dependent system, and both interact with Hsp70 chaperones...
  17. Garland S, Hoff K, Vickery L, Culotta V. Saccharomyces cerevisiae ISU1 and ISU2: members of a well-conserved gene family for iron-sulfur cluster assembly. J Mol Biol. 1999;294:897-907 pubmed
    ..This report focuses on two genes of bakers yeast Saccharomyces cerevisiae, ISU1 and ISU2, which encode homologues to bacterial IscU and NifU, potential iron-binding or cluster-assembly proteins...
  18. Pandey A, Gordon D, Pain J, Stemmler T, Dancis A, Pain D. Frataxin directly stimulates mitochondrial cysteine desulfurase by exposing substrate-binding sites, and a mutant Fe-S cluster scaffold protein with frataxin-bypassing ability acts similarly. J Biol Chem. 2013;288:36773-86 pubmed publisher
    ..This novel function of frataxin does not require iron, Isu1, or Isd11...
  19. Andrew A, Song J, Schilke B, Craig E. Posttranslational regulation of the scaffold for Fe-S cluster biogenesis, Isu. Mol Biol Cell. 2008;19:5259-66 pubmed publisher
    ..Our results are consistent with the existence of a mechanism to increase the stability of Isu, and thus its level, that is dependent on the presence of the cysteine desulfurase Nfs1. ..
  20. Saha P, Kumar S, Srivastava S, Sinha D, Pareek G, D Silva P. The presence of multiple cellular defects associated with a novel G50E iron-sulfur cluster scaffold protein (ISCU) mutation leads to development of mitochondrial myopathy. J Biol Chem. 2014;289:10359-77 pubmed publisher
    ..Thus, our findings provide compelling evidence that the respiration defect due to impaired biogenesis of Fe-S clusters in myopathy patients leads to manifestation of complex clinical symptoms. ..
  21. Leidgens S, De Smet S, Foury F. Frataxin interacts with Isu1 through a conserved tryptophan in its beta-sheet. Hum Mol Genet. 2010;19:276-86 pubmed publisher
    ..It has been shown that Yfh1, the yeast frataxin homologue, interacts functionally and physically with Isu1, the scaffold protein on which the Fe/S clusters are assembled...
  22. Ranatunga W, Gakh O, Galeano B, Smith D, Söderberg C, Al Karadaghi S, et al. Architecture of the Yeast Mitochondrial Iron-Sulfur Cluster Assembly Machinery: THE SUB-COMPLEX FORMED BY THE IRON DONOR, Yfh1 PROTEIN, AND THE SCAFFOLD, Isu1 PROTEIN. J Biol Chem. 2016;291:10378-98 pubmed publisher
    ..functional complex consisting of the iron donor, Yfh1 (yeast frataxin homologue 1), and the Fe-S cluster scaffold, Isu1, with 1:1 stoichiometry, [Yfh1]24·[Isu1]24 Using negative staining transmission EM and single particle analysis, ..
  23. Wang T, Craig E. Binding of yeast frataxin to the scaffold for Fe-S cluster biogenesis, Isu. J Biol Chem. 2008;283:12674-9 pubmed publisher
  24. Majewska J, Ciesielski S, Schilke B, Kominek J, Blenska A, Delewski W, et al. Binding of the chaperone Jac1 protein and cysteine desulfurase Nfs1 to the iron-sulfur cluster scaffold Isu protein is mutually exclusive. J Biol Chem. 2013;288:29134-42 pubmed publisher
    ..The results of molecular modeling of the Isu1-Jac1 interaction, which was guided by these experimental data and structural/biophysical information available for ..
  25. Webert H, Freibert S, Gallo A, Heidenreich T, Linne U, Amlacher S, et al. Functional reconstitution of mitochondrial Fe/S cluster synthesis on Isu1 reveals the involvement of ferredoxin. Nat Commun. 2014;5:5013 pubmed publisher
    ..In vivo synthesis of [2Fe-2S] clusters on the mitochondrial scaffold protein Isu1 requires the cysteine desulphurase complex Nfs1-Isd11, frataxin, ferredoxin Yah1 and its reductase Arh1...
  26. Gakh O, Smith D, Isaya G. Assembly of the iron-binding protein frataxin in Saccharomyces cerevisiae responds to dynamic changes in mitochondrial iron influx and stress level. J Biol Chem. 2008;283:31500-10 pubmed publisher
    ..from trimer to > or = 24-mer, independent of interactions between Yfh1 and its major iron-binding partners, Isu1/Nfs1 or aconitase...
  27. Gerber J, Neumann K, Prohl C, Muhlenhoff U, Lill R. The yeast scaffold proteins Isu1p and Isu2p are required inside mitochondria for maturation of cytosolic Fe/S proteins. Mol Cell Biol. 2004;24:4848-57 pubmed
    ..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. ..
  28. Li L, Miao R, Bertram S, Jia X, Ward D, Kaplan J. A role for iron-sulfur clusters in the regulation of transcription factor Yap5-dependent high iron transcriptional responses in yeast. J Biol Chem. 2012;287:35709-21 pubmed publisher
    ..that mutation or reduced expression of other genes involved in mitochondrial iron-sulfur cluster synthesis (YFH1, ISU1) prevented induction of the Yap5 response...
  29. Manicki M, Majewska J, Ciesielski S, Schilke B, Blenska A, Kominek J, et al. Overlapping binding sites of the frataxin homologue assembly factor and the heat shock protein 70 transfer factor on the Isu iron-sulfur cluster scaffold protein. J Biol Chem. 2014;289:30268-78 pubmed publisher