FXN:NFS1:ISD11:ISCU Synthesizes Iron-Sulfur Cluster Authored: Lill, R, 2012-09-24 Authored: May, B, 2011-06-04 EC Number: 2.8.1.7 Edited: May, B, 2011-06-04 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). Pubmed10639125 Pubmed12785837 Pubmed12886008 Pubmed12947415 Pubmed12970193 Pubmed15952888 Pubmed16847322 Pubmed17331979 Pubmed18319250 Pubmed18339629 Pubmed19454487 Pubmed20873749 Pubmed21944046 Pubmed22077971 Pubmed22101253 Pubmed22306468 Pubmed22352884 Pubmed22511353 Reactome Database ID Release 431362408 Reactome, http://www.reactome.org ReactomeREACT_150385 Reviewed: Rouault, TA, 2012-10-11 Reviewed: Tong, Wing-Hang, 2012-10-11 has a Stoichiometric coefficient of 4 FXN:NFS1:ISD11:ISCU:2Fe-2S Cluster FDX1/1L (reduced) FDX1/1L (oxidized) 2 Iron:FXN:NFS1:ISD11:ISCU