Search results for GLRX5

Showing 5 results out of 5

×

Species

Types

Compartments

Search properties

Species

Types

Compartments

Search properties

Protein (1 results from a total of 1)

Identifier: R-HSA-2564761
Species: Homo sapiens
Compartment: mitochondrial matrix
Primary external reference: UniProt: GLRX5: Q86SX6

Complex (1 results from a total of 1)

Identifier: R-HSA-8878793
Species: Homo sapiens
Compartment: mitochondrial matrix

Reaction (2 results from a total of 2)

Identifier: R-HSA-8878815
Species: Homo sapiens
Compartment: mitochondrial matrix
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).
Identifier: R-HSA-1362408
Species: Homo sapiens
Compartment: mitochondrial matrix
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 FDX2 (FDX1L) are required (Tong et al. 2003, Cai et al. 2017) and may reduce the sulfur from S0 to S2- (sulfide). 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).

Pathway (1 results from a total of 1)

Identifier: R-HSA-1362409
Species: Homo sapiens
Compartment: mitochondrial inner membrane, mitochondrial matrix, mitochondrial intermembrane space
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.
Cite Us!