5t0v

Structural highlights

Function

ISU1_YEAST Scaffold protein for the de novo synthesis of iron-sulfur (Fe-S) clusters within mitochondria, which is required for maturation of both mitochondrial and cytoplasmic [2Fe-2S] and [4Fe-4S] proteins. First, a [2Fe-2S] cluster is transiently assembled on the scaffold proteins ISU1 and ISU2. In a second step, the cluster is released from ISU1/ISU2, transferred to glutaredoxin GRX5, followed by the formation of mitochondrial [2Fe-2S] proteins, the synthesis of [4Fe-4S] clusters and their target-specific insertion into the recipient apoproteins. Cluster assembly on ISU1/ISU2 depends on the function of the cysteine desulfurase complex NFS1-ISD11, which serves as the sulfur donor for cluster synthesis, the iron-binding protein frataxin (YFH1) as the putative iron donor, and the electron transfer chain comprised of ferredoxin reductase ARH1 and ferredoxin YAH1, which receive their electrons from NADH. Fe-S cluster release from ISU1/ISU2 is achieved by interaction with the Hsp70 chaperone SSQ1, assisted by the DnaJ-like co-chaperone JAC1 and the nucleotide exchange factor MGE1. ISU1 is the major isoform in yeast, while ISU2 is not detectable in cells grown to stationary phase (PubMed:10588895, PubMed:12970193, PubMed:14741370, PubMed:15123690, PubMed:16341089, PubMed:16431909, PubMed:23615440, PubMed:25358379).^{[1] [2] [3] [4] [5] [6] [7] [8]}

See Also

• Frataxin 3D Structures

References

1. ↑ Garland SA, Hoff K, Vickery LE, Culotta VC. Saccharomyces cerevisiae ISU1 and ISU2: members of a well-conserved gene family for iron-sulfur cluster assembly. J Mol Biol. 1999 Dec 10;294(4):897-907. PMID:10588895 doi:http://dx.doi.org/10.1006/jmbi.1999.3294
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 Sep 15;22(18):4815-25. PMID:12970193 doi:http://dx.doi.org/10.1093/emboj/cdg446
3. ↑ 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 Jan 16;557(1-3):215-20. PMID:14741370
4. ↑ Dutkiewicz R, Schilke B, Cheng S, Knieszner H, Craig EA, 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 Jul 9;279(28):29167-74. Epub 2004 Apr 30. PMID:15123690 doi:10.1074/jbc.M402947200
5. ↑ Wiedemann N, Urzica E, Guiard B, Muller H, Lohaus C, Meyer HE, Ryan MT, Meisinger C, Muhlenhoff U, Lill R, Pfanner N. Essential role of Isd11 in mitochondrial iron-sulfur cluster synthesis on Isu scaffold proteins. EMBO J. 2006 Jan 11;25(1):184-95. Epub 2005 Dec 8. PMID:16341089 doi:http://dx.doi.org/10.1038/sj.emboj.7600906
6. ↑ Dutkiewicz R, Marszalek J, Schilke B, Craig EA, Lill R, Muhlenhoff U. The Hsp70 chaperone Ssq1p is dispensable for iron-sulfur cluster formation on the scaffold protein Isu1p. J Biol Chem. 2006 Mar 24;281(12):7801-8. Epub 2006 Jan 23. PMID:16431909 doi:M513301200
7. ↑ Uzarska MA, Dutkiewicz R, Freibert SA, 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 Jun;24(12):1830-41. doi: 10.1091/mbc.E12-09-0644. Epub 2013, Apr 24. PMID:23615440 doi:http://dx.doi.org/10.1091/mbc.E12-09-0644
8. ↑ Webert H, Freibert SA, Gallo A, Heidenreich T, Linne U, Amlacher S, Hurt E, Muhlenhoff U, Banci L, Lill R. Functional reconstitution of mitochondrial Fe/S cluster synthesis on Isu1 reveals the involvement of ferredoxin. Nat Commun. 2014 Oct 31;5:5013. doi: 10.1038/ncomms6013. PMID:25358379 doi:http://dx.doi.org/10.1038/ncomms6013