Mitochondrial iron-sulfur cluster biogenesis (Homo sapiens)

From WikiPathways

Jump to: navigation, search
2, 8, 11, 13, 19...91, 18, 20, 27, 35...4, 13, 14, 16, 22...3, 5-7, 10...34, 37cytosolmitochondrial intermembrane spacemitochondrial matrixPXLP FXN(81-210) ISCU-1 SLC25A28 FXN(81-210) L-CysISCA2 ISCA2 FDX1L NADPHFe2+FDX1 NFS1-1 FDX1,FDX1L (red.)H+NADP+FDX1 Fe2+HSCBSLC25A37 2Fe-2S cluster 4Fe-4S cluster ISCU-1 ISCA1:ISCA2Mitoferrin1,2GLRX5:2Fe-2SFDXR Fe2+ FADH2 GLRX5 NFS1-1 L-AlaPXLP FAD ISCA1 LYRM4 ISCA1 FDXR:FADISCU-1 (2Fe-2S)(1+) GLRX5FDX1L ISCA1:ISCA2:4Fe-4SFXN:NFS1:ISD11:ISCU:2Fe-2S Cluster(2Fe-2S)2+ FXN:ISD11:NFS1:ISCU2Iron:FXN:NFS1:ISD11:ISCUPXLP NFS1-1 2Fe-2S cluster FDX1,FDX1L (ox.)FDXR LYRM4 FXN(81-210) FDXR:FADH2LYRM4 4, 24, 26, 404, 16, 24, 26, 40184, 16, 22, 24, 26...18


Iron-sulfur (Fe-S) proteins are localized in the cytosol, nucleus, and mitochondria of mammalian cells (reviewed in Stemmler et al. 2010, Rouault 2012, Bandyopadhyay et al. 2008, Lill 2009, Lill et al. 2012). Fe-S protein biogenesis in the mitochondrial matrix involves the iron-sulfur cluster (ISC) assembly machinery. Ferrous iron is transported across the inner mitochondrial membrane into the mitochondrial matrix by Mitoferrin-1 (SLC25A37) and Mitoferrin-2 (SLC25A28). (Mitoferrin-1 is enriched in erythroid cells while Mitoferrin-2 is ubiquitous.) Frataxin binds ferrous iron in the mitochondrial matrix. The cysteine desulfurase NFS1 in a subcomplex with ISD11 provides the sulfur by converting cyteine into alanine and forming a persulfide which is used for cluster formation on ISCU, the scaffold protein. Interaction between NFS1 and ISD11 is necessary for desulfurase activity. Frataxin binds to a complex containing NFS1, ISD11, and ISCU and is proposed to function as an iron donor to ISCU or as an allosteric switch that activates sulfur transfer and Fe-S cluster assembly (Tsai and Barondeau 2010). Cluster formation also involves the electron transfer chain ferredoxin reductase and ferredoxin. ISCU initially forms clusters containing 2 iron atoms and 2 sulfur atoms ([2Fe-2S] clusters). They are released by the function of HSP70-HSC20 chaperones and the monothiol glutaredoxin GLRX5 and used for assembly of [2Fe-2S] proteins. Assembly of larger clusters such as [4Fe-4S] clusters may involve the function of ISCA1, ISCA2, and IBA57. The clusters are transferred to apo-enzymes such as the respiratory complexes, aconitase, and lipoate synthase through dedicated targeting factors such as IND1, NFU1, and BOLA3. View original pathway at:Reactome.


Pathway is converted from Reactome ID: 1362409
Reactome version: 66
Reactome Author 
Reactome Author: Lill, R

Quality Tags

Ontology Terms



View all...
  1. Uhrigshardt H, Singh A, Kovtunovych G, Ghosh M, Rouault TA.; ''Characterization of the human HSC20, an unusual DnaJ type III protein, involved in iron-sulfur cluster biogenesis.''; PubMed Europe PMC Scholia
  2. Stehling O, Lill R.; ''The role of mitochondria in cellular iron-sulfur protein biogenesis: mechanisms, connected processes, and diseases.''; PubMed Europe PMC Scholia
  3. Navarro-Sastre A, Tort F, Stehling O, Uzarska MA, Arranz JA, Del Toro M, Labayru MT, Landa J, Font A, Garcia-Villoria J, Merinero B, Ugarte M, Gutierrez-Solana LG, Campistol J, Garcia-Cazorla A, Vaquerizo J, Riudor E, Briones P, Elpeleg O, Ribes A, Lill R.; ''A fatal mitochondrial disease is associated with defective NFU1 function in the maturation of a subset of mitochondrial Fe-S proteins.''; PubMed Europe PMC Scholia
  4. Schmucker S, Martelli A, Colin F, Page A, Wattenhofer-Donzé M, Reutenauer L, Puccio H.; ''Mammalian frataxin: an essential function for cellular viability through an interaction with a preformed ISCU/NFS1/ISD11 iron-sulfur assembly complex.''; PubMed Europe PMC Scholia
  5. Yuvaniyama P, Agar JN, Cash VL, Johnson MK, Dean DR.; ''NifS-directed assembly of a transient [2Fe-2S] cluster within the NifU protein.''; PubMed Europe PMC Scholia
  6. Fox NG, Das D, Chakrabarti M, Lindahl PA, Barondeau DP.; ''Frataxin Accelerates [2Fe-2S] Cluster Formation on the Human Fe-S Assembly Complex.''; PubMed Europe PMC Scholia
  7. Bridwell-Rabb J, Iannuzzi C, Pastore A, Barondeau DP.; ''Effector role reversal during evolution: the case of frataxin in Fe-S cluster biosynthesis.''; PubMed Europe PMC Scholia
  8. Lill R.; ''Function and biogenesis of iron-sulphur proteins.''; PubMed Europe PMC Scholia
  9. Brandt ME, Vickery LE.; ''Expression and characterization of human mitochondrial ferredoxin reductase in Escherichia coli.''; PubMed Europe PMC Scholia
  10. Johnson DC, Dean DR, Smith AD, Johnson MK.; ''Structure, function, and formation of biological iron-sulfur clusters.''; PubMed Europe PMC Scholia
  11. Rouault TA.; ''Biogenesis of iron-sulfur clusters in mammalian cells: new insights and relevance to human disease.''; PubMed Europe PMC Scholia
  12. Fox NG, Chakrabarti M, McCormick SP, Lindahl PA, Barondeau DP.; ''The Human Iron-Sulfur Assembly Complex Catalyzes the Synthesis of [2Fe-2S] Clusters on ISCU2 That Can Be Transferred to Acceptor Molecules.''; PubMed Europe PMC Scholia
  13. Stemmler TL, Lesuisse E, Pain D, Dancis A.; ''Frataxin and mitochondrial FeS cluster biogenesis.''; PubMed Europe PMC Scholia
  14. Stehling O, Elsässer HP, Brückel B, Mühlenhoff U, Lill R.; ''Iron-sulfur protein maturation in human cells: evidence for a function of frataxin.''; PubMed Europe PMC Scholia
  15. Wang T, Craig EA.; ''Binding of yeast frataxin to the scaffold for Fe-S cluster biogenesis, Isu.''; PubMed Europe PMC Scholia
  16. Yoon T, Cowan JA.; ''Iron-sulfur cluster biosynthesis. Characterization of frataxin as an iron donor for assembly of [2Fe-2S] clusters in ISU-type proteins.''; PubMed Europe PMC Scholia
  17. Bandyopadhyay S, Naik SG, O'Carroll IP, Huynh BH, Dean DR, Johnson MK, Dos Santos PC.; ''A proposed role for the Azotobacter vinelandii NfuA protein as an intermediate iron-sulfur cluster carrier.''; PubMed Europe PMC Scholia
  18. Brancaccio D, Gallo A, Mikolajczyk M, Zovo K, Palumaa P, Novellino E, Piccioli M, Ciofi-Baffoni S, Banci L.; ''Formation of [4Fe-4S] clusters in the mitochondrial iron-sulfur cluster assembly machinery.''; PubMed Europe PMC Scholia
  19. Bandyopadhyay S, Chandramouli K, Johnson MK.; ''Iron-sulfur cluster biosynthesis.''; PubMed Europe PMC Scholia
  20. Sheftel AD, Wilbrecht C, Stehling O, Niggemeyer B, Elsässer HP, Mühlenhoff U, Lill R.; ''The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe-4S] protein maturation.''; PubMed Europe PMC Scholia
  21. Mühlenhoff U, Gerber J, Richhardt N, Lill R.; ''Components involved in assembly and dislocation of iron-sulfur clusters on the scaffold protein Isu1p.''; PubMed Europe PMC Scholia
  22. Cavadini P, O'Neill HA, Benada O, Isaya G.; ''Assembly and iron-binding properties of human frataxin, the protein deficient in Friedreich ataxia.''; PubMed Europe PMC Scholia
  23. Biederbick A, Stehling O, Rösser R, Niggemeyer B, Nakai Y, Elsässer HP, Lill R.; ''Role of human mitochondrial Nfs1 in cytosolic iron-sulfur protein biogenesis and iron regulation.''; PubMed Europe PMC Scholia
  24. Tsai CL, Barondeau DP.; ''Human frataxin is an allosteric switch that activates the Fe-S cluster biosynthetic complex.''; PubMed Europe PMC Scholia
  25. Bridwell-Rabb J, Winn AM, Barondeau DP.; ''Structure-function analysis of Friedreich's ataxia mutants reveals determinants of frataxin binding and activation of the Fe-S assembly complex.''; PubMed Europe PMC Scholia
  26. Shan Y, Napoli E, Cortopassi G.; ''Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones.''; PubMed Europe PMC Scholia
  27. Banci L, Brancaccio D, Ciofi-Baffoni S, Del Conte R, Gadepalli R, Mikolajczyk M, Neri S, Piccioli M, Winkelmann J.; ''[2Fe-2S] cluster transfer in iron-sulfur protein biogenesis.''; PubMed Europe PMC Scholia
  28. Tong WH, Jameson GN, Huynh BH, Rouault TA.; ''Subcellular compartmentalization of human Nfu, an iron-sulfur cluster scaffold protein, and its ability to assemble a [4Fe-4S] cluster.''; PubMed Europe PMC Scholia
  29. Lill R, Hoffmann B, Molik S, Pierik AJ, Rietzschel N, Stehling O, Uzarska MA, Webert H, Wilbrecht C, Mühlenhoff U.; ''The role of mitochondria in cellular iron-sulfur protein biogenesis and iron metabolism.''; PubMed Europe PMC Scholia
  30. Cameron JM, Janer A, Levandovskiy V, Mackay N, Rouault TA, Tong WH, Ogilvie I, Shoubridge EA, Robinson BH.; ''Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes.''; PubMed Europe PMC Scholia
  31. Shi Y, Ghosh MC, Tong WH, Rouault TA.; ''Human ISD11 is essential for both iron-sulfur cluster assembly and maintenance of normal cellular iron homeostasis.''; PubMed Europe PMC Scholia
  32. Sheftel A, Stehling O, Lill R.; ''Iron-sulfur proteins in health and disease.''; PubMed Europe PMC Scholia
  33. Huang J, Dizin E, Cowan JA.; ''Mapping iron binding sites on human frataxin: implications for cluster assembly on the ISU Fe-S cluster scaffold protein.''; PubMed Europe PMC Scholia
  34. Sheftel AD, Stehling O, Pierik AJ, Elsässer HP, Mühlenhoff U, Webert H, Hobler A, Hannemann F, Bernhardt R, Lill R.; ''Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe/S cluster biosynthesis.''; PubMed Europe PMC Scholia
  35. Brancaccio D, Gallo A, Piccioli M, Novellino E, Ciofi-Baffoni S, Banci L.; ''[4Fe-4S] Cluster Assembly in Mitochondria and Its Impairment by Copper.''; PubMed Europe PMC Scholia
  36. Gerber J, Mühlenhoff U, Lill R.; ''An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1.''; PubMed Europe PMC Scholia
  37. Shi Y, Ghosh M, Kovtunovych G, Crooks DR, Rouault TA.; ''Both human ferredoxins 1 and 2 and ferredoxin reductase are important for iron-sulfur cluster biogenesis.''; PubMed Europe PMC Scholia
  38. Marinoni EN, de Oliveira JS, Nicolet Y, Raulfs EC, Amara P, Dean DR, Fontecilla-Camps JC.; ''(IscS-IscU)2 complex structures provide insights into Fe2S2 biogenesis and transfer.''; PubMed Europe PMC Scholia
  39. Mühlenhoff U, Richter N, Pines O, Pierik AJ, Lill R.; ''Specialized function of yeast Isa1 and Isa2 proteins in the maturation of mitochondrial [4Fe-4S] proteins.''; PubMed Europe PMC Scholia
  40. Tong WH, Rouault T.; ''Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells.''; PubMed Europe PMC Scholia
  41. Ciesielski SJ, Schilke BA, Osipiuk J, Bigelow L, Mulligan R, Majewska J, Joachimiak A, Marszalek J, Craig EA, Dutkiewicz R.; ''Interaction of J-protein co-chaperone Jac1 with Fe-S scaffold Isu is indispensable in vivo and conserved in evolution.''; PubMed Europe PMC Scholia


View all...
101454view11:32, 1 November 2018ReactomeTeamreactome version 66
100992view21:11, 31 October 2018ReactomeTeamreactome version 65
100528view19:45, 31 October 2018ReactomeTeamreactome version 64
100075view16:28, 31 October 2018ReactomeTeamreactome version 63
99626view15:01, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93991view13:50, 16 August 2017ReactomeTeamreactome version 61
93599view11:28, 9 August 2017ReactomeTeamreactome version 61
87954view13:07, 25 July 2016RyanmillerOntology Term : 'classic metabolic pathway' added !
86706view09:24, 11 July 2016ReactomeTeamreactome version 56
83054view09:47, 18 November 2015ReactomeTeamVersion54
81756view09:56, 26 August 2015ReactomeTeamVersion53
76911view08:18, 17 July 2014ReactomeTeamFixed remaining interactions
76616view11:59, 16 July 2014ReactomeTeamFixed remaining interactions
75947view10:00, 11 June 2014ReactomeTeamRe-fixing comment source
75650view10:54, 10 June 2014ReactomeTeamReactome 48 Update
75005view13:52, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74649view08:42, 30 April 2014ReactomeTeamNew pathway

External references


View all...
NameTypeDatabase referenceComment
(2Fe-2S)(1+) MetaboliteCHEBI:33738 (ChEBI)
(2Fe-2S)2+ MetaboliteCHEBI:33737 (ChEBI)
2 Iron:FXN:NFS1:ISD11:ISCUComplexR-HSA-1362401 (Reactome)
2Fe-2S cluster MetaboliteCHEBI:33739 (ChEBI)
4Fe-4S cluster MetaboliteCHEBI:49883 (ChEBI)
FAD MetaboliteCHEBI:16238 (ChEBI)
FADH2 MetaboliteCHEBI:17877 (ChEBI)
FDX1 ProteinP10109 (Uniprot-TrEMBL)
FDX1,FDX1L (ox.)ComplexR-HSA-2408370 (Reactome)
FDX1,FDX1L (red.)ComplexR-HSA-2408372 (Reactome)
FDX1L ProteinQ6P4F2 (Uniprot-TrEMBL)
FDXR ProteinP22570 (Uniprot-TrEMBL)
FDXR:FADH2ComplexR-HSA-2395502 (Reactome)
FDXR:FADComplexR-HSA-2395508 (Reactome)
FXN(81-210) ProteinQ16595 (Uniprot-TrEMBL)
FXN:ISD11:NFS1:ISCUComplexR-HSA-1362404 (Reactome)
FXN:NFS1:ISD11:ISCU:2Fe-2S ClusterComplexR-HSA-1362398 (Reactome)
Fe2+ MetaboliteCHEBI:18248 (ChEBI)
Fe2+MetaboliteCHEBI:18248 (ChEBI)
GLRX5 ProteinQ86SX6 (Uniprot-TrEMBL)
GLRX5:2Fe-2SComplexR-HSA-8878793 (Reactome)
GLRX5ProteinQ86SX6 (Uniprot-TrEMBL)
H+MetaboliteCHEBI:15378 (ChEBI)
HSCBProteinQ8IWL3 (Uniprot-TrEMBL)
ISCA1 ProteinQ9BUE6 (Uniprot-TrEMBL)
ISCA1:ISCA2:4Fe-4SComplexR-HSA-8878796 (Reactome)
ISCA1:ISCA2ComplexR-HSA-8878840 (Reactome)
ISCA2 ProteinQ86U28 (Uniprot-TrEMBL)
ISCU-1 ProteinQ9H1K1-1 (Uniprot-TrEMBL)
L-AlaMetaboliteCHEBI:57972 (ChEBI)
L-CysMetaboliteCHEBI:35235 (ChEBI)
LYRM4 ProteinQ9HD34 (Uniprot-TrEMBL)
Mitoferrin1,2ComplexR-HSA-1362399 (Reactome)
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPHMetaboliteCHEBI:16474 (ChEBI)
NFS1-1 ProteinQ9Y697-1 (Uniprot-TrEMBL) By analogy with yeast Hfs1, human NFS1 probably has an N-terminal transit peptide that is removed by mitochondrial processing peptidase. The cleavage site is unknown.
PXLP MetaboliteCHEBI:18405 (ChEBI)
SLC25A28 ProteinQ96A46 (Uniprot-TrEMBL)
SLC25A37 ProteinQ9NYZ2 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
2 Iron:FXN:NFS1:ISD11:ISCUArrowR-HSA-1362416 (Reactome)
2 Iron:FXN:NFS1:ISD11:ISCUR-HSA-1362408 (Reactome)
2 Iron:FXN:NFS1:ISD11:ISCUmim-catalysisR-HSA-1362408 (Reactome)
FDX1,FDX1L (ox.)ArrowR-HSA-1362408 (Reactome)
FDX1,FDX1L (ox.)R-HSA-2395512 (Reactome)
FDX1,FDX1L (red.)ArrowR-HSA-1362408 (Reactome)
FDX1,FDX1L (red.)ArrowR-HSA-2395512 (Reactome)
FDX1,FDX1L (red.)R-HSA-1362408 (Reactome)
FDX1,FDX1L (red.)mim-catalysisR-HSA-1362408 (Reactome)
FDXR:FADArrowR-HSA-2395512 (Reactome)
FDXR:FADH2ArrowR-HSA-2395517 (Reactome)
FDXR:FADH2R-HSA-2395512 (Reactome)
FDXR:FADR-HSA-2395517 (Reactome)
FXN:ISD11:NFS1:ISCUR-HSA-1362416 (Reactome)
FXN:NFS1:ISD11:ISCU:2Fe-2S ClusterArrowR-HSA-1362408 (Reactome)
Fe2+ArrowR-HSA-1362417 (Reactome)
Fe2+R-HSA-1362416 (Reactome)
Fe2+R-HSA-1362417 (Reactome)
GLRX5:2Fe-2SR-HSA-8878815 (Reactome)
GLRX5ArrowR-HSA-8878815 (Reactome)
H+ArrowR-HSA-2395512 (Reactome)
H+R-HSA-2395517 (Reactome)
HSCBArrowR-HSA-8878815 (Reactome)
ISCA1:ISCA2:4Fe-4SArrowR-HSA-8878815 (Reactome)
ISCA1:ISCA2R-HSA-8878815 (Reactome)
L-AlaArrowR-HSA-1362408 (Reactome)
L-CysR-HSA-1362408 (Reactome)
Mitoferrin1,2mim-catalysisR-HSA-1362417 (Reactome)
NADP+ArrowR-HSA-2395517 (Reactome)
NADPHR-HSA-2395517 (Reactome)
R-HSA-1362408 (Reactome) Iron-sulfur clusters are assembled on the scaffold, ISCU. Based on homology with bacterial IscU:IscS complexes (reviewed in Johnson et al. 2005), one molecule of ISCU is bound to each subunit of a NFS1 dimer (Marinoni et al. 2012). A single complex may thus be capable of assembling two 2Fe-2S clusters. Sulfide is provided by desulfuration of cysteine by NFS1:ISD11 (Biederbick et al. 2006, Shi et al. 2009, Tsai and Barondeau 2010). It has been proposed that ferrous iron is delivered by FXN (Gerber et al. 2003, Yoon and Cowan 2003, Schmucker et al. 2011) bound to ISCU (inferred from yeast, Wang and Craig 2008), although more recent studies suggested that FXN functions as an allosteric effector to stimulate sulfide transfer (Tsai et al. 2010). Holo-ISCU (ISCU bound to a newly synthesized 2Fe-2S cluster) transiently interacts with a dedicated HSP70 chaperone system including Mortalin (GRP75) and HSP20 and GLRX5 (GRX5). Electrons supplied by FDXL1 (FDX2) are required and may reduce the sulfur from S0 to S2-. NFU1 binds an Fe-S cluster (Tong et al. 2003, inferred from bacteria Yuvaniyama et al. 2000) and, from biochemical studies of bacterial NFU1 homologues, is proposed to be an intermediate Fe-S cluster carrier (Bandyopadhy et al. 2008). Mutations in human NFU1 affect only a subset of Fe-S proteins (Navarro-Sastre et al. 2011).
R-HSA-1362416 (Reactome) Frataxin (FXN) specifically binds 2 atoms of ferrous iron per monomer (reviewed in Stemmler et al. 2010). Iron bound to Frataxin may (Yoon and Cowan 2003, Gerber et al. 2003) or may not (Schmucker et al. 2011) enhance the interaction of Frataxin with NFS1, ICSU, and ISD11. Frataxin was shown to stimulate the cysteine desulfurase activity of NFS1 and was proposed to be a regulator of sulfur production (Tsai et al. 2010). The formation of sulfide by NFS1 is most efficiently observed when NFS1 is in complex with ISD11, ISCU, and FXN in the presence of cysteine and iron. This means that only the complete system of NFS1, ISD11, ISCU, FXN, cysteine, and iron is fully active as a desulfurase. FXN therefore seems to be a regulator of the cysteine desulfurase permitting sulfide production only when all components needed for Fe-S cluster synthesis are present and the ISCU-bound Fe-S cluster can be formed.
R-HSA-1362417 (Reactome) As inferred from biochemical studies in yeast and phenotypic studies in mouse, Mitoferrin-1 (SLC25A37) and Mitoferrin-2 (SLC25A28) transport ferrous iron across the inner mitochondrial membrane. Mitoferrin-1 is essential for maintaining mitochondrial iron uptake in developing erythroid cells; mitoferrin-2 is ubiquitously expressed. Defects in Mitoferrin-1 and Mitoferrin-2 cause a reduction in mitochondrial iron acquisition and biogenesis of iron-sulfur clusters and heme.
R-HSA-2395512 (Reactome) Two electrons are transferred from reduced ferredoxin reductase (FDXR, adrenodoxin reductase) to two ferredoxin-1 or ferredoxin-1L (FDX1, FDX1L) molecules, each of which binds one electron. Two protons are released during the reaction.
R-HSA-2395517 (Reactome) Two electrons and one proton are transferred from NADPH to the FAD moiety of ferredoxin reductase. A proton from the medium is also taken up by ferredoxin reductase.
R-HSA-8878815 (Reactome) Iron-sulfur clusters containing 4Fe-4S are assembled from 2Fe-2S clusters on ISCA1:ISCA2 heterodimers (Banci et al. 2014, Brancaccio et al. 2014, inferred from Saccharomyces cerevisiae in Mühlenhoff et al. 2011). GLRX5:2Fe-2S can donate 2Fe-2S clusters to ISCA1:ISCA2 in vitro (Banci et al. 2014, Brancaccio et al. 2014). It is unclear if other proteins also donate 2Fe-2S clusters. Two conserved C-terminal cysteines of ISCA1:ISCA2 heterodimers extract [2Fe-2S] clusters from GLRX5, forming a ISCA1:ISCA2:GLRX5 intermediate containing two 2Fe-2S clusters (Brancaccio et al. 2017). The physiological electron donor required to convert the two 2Fe-2S clusters bound to the intermediate into a 4Fe-4S cluster is not yet characterized. ISCA1, ISCA2, and IBA57 are required for formation of holoenzymes such as aconitase that contain 4Fe-4S clusters (Sheftel et al. 2012). HSCB (HSC20), the homolog of yeast JAC1, interacts with HSPA9 and appears to facilitate the reaction (Uhrigshardt et al. 2010).
Personal tools