Mitochondrial iron-sulfur cluster biogenesis (Homo sapiens)

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<?xml version="1.0" encoding="UTF-8"?> <Pathway xmlns="http://pathvisio.org/GPML/2013a" Name="Mitochondrial iron-sulfur cluster biogenesis" Organism="Homo sapiens"> <Comment Source="WikiPathways-description">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. 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/> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="240.0" CenterY="830.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P10109" /> </DataNode> <DataNode TextLabel="ISCA2 " GraphId="ceec2" Type="Protein" GroupRef="fc037"> <Attribute Key="cellular_location" Value="mitochondrial matrix" /> <Attribute Key="complex_id" Value="R-HSA-8878796" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="240.0" CenterY="1210.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q86U28" /> </DataNode> <DataNode TextLabel="L-Cys" GraphId="cfe7b" Type="Metabolite"> <Attribute Key="cellular_location" Value="mitochondrial matrix" /> <Graphics CenterX="241.5" CenterY="326.0" Width="85.0" Height="28.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:35235" /> </DataNode> <DataNode TextLabel="2Fe-2S cluster " GraphId="d0175" Type="Metabolite" GroupRef="e9424"> <Attribute Key="cellular_location" Value="mitochondrial matrix" /> <Attribute Key="complex_id" Value="R-HSA-8878793" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="240.0" CenterY="1050.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:33739" /> </DataNode> <DataNode TextLabel="PXLP-K258-NFS1-1 " GraphId="d0222" Type="Protein" GroupRef="bae05"> <Comment Source="Reactome">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.</Comment> <Attribute Key="cellular_location" Value="mitochondrial matrix" /> <Attribute Key="complex_id" Value="R-HSA-1362404" /> <Attribute Key="copies_num" Value="5" /> <Graphics CenterX="100.0" CenterY="930.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9Y697-1" /> </DataNode> <DataNode TextLabel="SLC25A37 " GraphId="d19f9" Type="Protein" GroupRef="e7b4d"> <Attribute Key="cellular_location" Value="mitochondrial inner membrane" /> <Attribute Key="complex_id" Value="R-HSA-1362399" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="100.0" CenterY="790.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9NYZ2" /> </DataNode> <DataNode TextLabel="FADH2 " GraphId="d21fd" Type="Metabolite" GroupRef="d5a8f"> <Attribute Key="cellular_location" Value="mitochondrial matrix" /> <Attribute Key="complex_id" Value="R-HSA-2395502" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="100.0" CenterY="1350.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" Color="0000ff" /> <Xref Database="ChEBI" ID="CHEBI:17877" /> </DataNode> <DataNode TextLabel="ISCA2 " GraphId="d4882" Type="Protein" GroupRef="a8458"> <Attribute Key="cellular_location" Value="mitochondrial matrix" /> <Attribute Key="complex_id" Value="R-HSA-8878840" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="240.0" CenterY="1130.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q86U28" /> </DataNode> <DataNode TextLabel="PXLP-K258-NFS1-1 " GraphId="d4e93" Type="Protein" GroupRef="ce13b"> <Comment Source="Reactome">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.</Comment> <Attribute Key="cellular_location" Value="mitochondrial matrix" /> <Attribute Key="complex_id" Value="R-HSA-1362401" /> <Attribute Key="copies_num" Value="8" /> <Graphics CenterX="100.0" CenterY="1070.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="Q9Y697-1" /> </DataNode> <DataNode TextLabel="FDX1 " GraphId="d8dd8" Type="Protein" GroupRef="ff3ad"> <Attribute Key="cellular_location" Value="mitochondrial matrix" /> <Attribute Key="complex_id" Value="R-HSA-2408372" /> <Attribute Key="copies_num" Value="1" /> <Graphics CenterX="240.0" CenterY="930.0" Width="100.0" Height="20.0" ZOrder="32768" FontSize="10" Valign="Middle" /> <Xref Database="Uniprot-TrEMBL" ID="P10109" /> </DataNode> <DataNode TextLabel="FXN:ISD11:NFS1:ISCU" GraphId="d8f1f" Type="Complex"> <BiopaxRef>e86</BiopaxRef> <BiopaxRef>aab</BiopaxRef> <BiopaxRef>d36</BiopaxRef> <BiopaxRef>a1e</BiopaxRef> <Attribute 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TextLabel="PXLP-K258-NFS1-1 " GraphId="ed5f5" Type="Protein" GroupRef="d7d84"> <Comment Source="Reactome">By analogy with yeast Hfs1, human NFS1 probably has an N-terminal transit peptide that is removed by mitochondrial processing peptidase. 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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).</Comment> <BiopaxRef>dcf</BiopaxRef> <BiopaxRef>e02</BiopaxRef> <BiopaxRef>fd1</BiopaxRef> <BiopaxRef>ffb</BiopaxRef> <BiopaxRef>fad</BiopaxRef> <BiopaxRef>e8d</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="565.0" Y="609.0" /> <Point X="628.0" Y="608.0" /> <Anchor Position="0.0" Shape="None" GraphId="d7404" /> <Anchor Position="0.99" Shape="None" GraphId="bf8a6" /> <Anchor Position="0.5" Shape="None" GraphId="cc304" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8878815" /> </Interaction> <Interaction GraphId="af808"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="591.0" Y="441.0" GraphRef="a1cd5" RelX="1.0" RelY="-0.037037037037037035" /> <Point X="631.0" Y="409.0" GraphRef="ee1ea" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2395512" /> </Interaction> <Interaction GraphId="b50ec"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="346.0" Y="428.0" GraphRef="eb488" RelX="0.0" RelY="0.7799999999999727" /> <Point X="431.0" Y="441.0" GraphRef="a1cd5" RelX="-1.0" RelY="-0.037037037037037035" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1362408" /> </Interaction> <Interaction GraphId="b5958"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="176.0" Y="160.0" GraphRef="b2e05" RelX="-0.011494252873563218" RelY="0.9459459459459459" /> <Point X="176.0" Y="208.0" GraphRef="df17d" RelX="-9.0" RelY="-0.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1362417" /> </Interaction> <Interaction GraphId="b6f57"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="683.0" Y="173.0" GraphRef="c644a" RelX="0.9710144927536232" RelY="0.0" /> <Point X="693.0" Y="239.0" GraphRef="b7841" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2395517" /> </Interaction> <Interaction GraphId="b79b9"> <Comment Source="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.</Comment> <BiopaxRef>eb6</BiopaxRef> <BiopaxRef>acc</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="631.0" Y="409.0" /> <Point X="629.0" Y="313.0" /> <Anchor Position="0.0" Shape="None" GraphId="ee1ea" /> <Anchor Position="0.99" Shape="None" GraphId="a7a27" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2395512" /> </Interaction> <Interaction GraphId="b7cfb"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="674.0" Y="236.0" GraphRef="e0bf9" RelX="1.0" RelY="0.0" /> <Point X="693.0" Y="239.0" GraphRef="b7841" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2395517" /> </Interaction> <Interaction GraphId="b8222"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="417.0" Y="346.0" GraphRef="d9f5f" RelX="-1.0" RelY="0.0" /> <Point X="344.0" Y="384.0" GraphRef="d6a82" RelX="-2.0" RelY="-5.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1362408" /> </Interaction> <Interaction GraphId="bf0ad"> <Comment Source="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 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).</Comment> <BiopaxRef>aab</BiopaxRef> <BiopaxRef>e48</BiopaxRef> <BiopaxRef>d36</BiopaxRef> <BiopaxRef>d8d</BiopaxRef> <BiopaxRef>e0d</BiopaxRef> <BiopaxRef>eb6</BiopaxRef> <BiopaxRef>db0</BiopaxRef> <BiopaxRef>ed5</BiopaxRef> <BiopaxRef>be5</BiopaxRef> <BiopaxRef>c1d</BiopaxRef> <BiopaxRef>ed1</BiopaxRef> <BiopaxRef>cde</BiopaxRef> <BiopaxRef>cad</BiopaxRef> <BiopaxRef>aec</BiopaxRef> <BiopaxRef>cb7</BiopaxRef> <BiopaxRef>d8e</BiopaxRef> <BiopaxRef>c21</BiopaxRef> <BiopaxRef>e19</BiopaxRef> <BiopaxRef>c39</BiopaxRef> <BiopaxRef>bd4</BiopaxRef> <BiopaxRef>a20</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="346.0" Y="350.0" /> <Point X="346.0" Y="428.0" /> <Anchor Position="0.0" Shape="None" GraphId="bafc3" /> <Anchor Position="0.99" Shape="None" GraphId="eb488" /> <Anchor Position="0.5" Shape="None" GraphId="cbf21" /> <Anchor Position="0.5" 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RelY="-0.03225806451612903" /> <Point X="149.0" Y="208.0" GraphRef="dd910" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1362417" /> </Interaction> <Interaction GraphId="cb694"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="628.0" Y="608.0" GraphRef="bf8a6" RelX="0.6299999999999955" RelY="-0.009999999999990905" /> <Point X="656.0" Y="620.0" GraphRef="fcfb2" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8878815" /> </Interaction> <Interaction GraphId="ccf84"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="476.0" Y="608.0" GraphRef="bda4e" RelX="1.0" RelY="0.0" /> <Point X="565.0" Y="609.0" GraphRef="d7404" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8878815" /> </Interaction> <Interaction GraphId="cd72d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="629.0" Y="313.0" GraphRef="a7a27" RelX="-0.01999999999998181" RelY="-0.9600000000000364" /> <Point X="656.0" Y="251.0" GraphRef="e0bf9" RelX="0.0" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2395512" /> </Interaction> <Interaction GraphId="cd94b"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="562.0" Y="561.0" GraphRef="bdb6a" RelX="0.9809523809523809" RelY="0.0" /> <Point X="565.0" Y="609.0" GraphRef="d7404" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8878815" /> </Interaction> <Interaction GraphId="cfe87"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="413.0" Y="154.0" GraphRef="d8f1f" RelX="0.0" RelY="1.0" /> <Point X="379.0" Y="213.0" GraphRef="a075b" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1362416" /> </Interaction> <Interaction GraphId="d98e5"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="698.0" Y="300.0" GraphRef="ed69a" RelX="0.049999999999954525" RelY="0.6100000000000136" /> <Point X="715.0" Y="353.0" GraphRef="f0670" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-2395517" /> </Interaction> <Interaction GraphId="da18f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="346.0" Y="428.0" GraphRef="eb488" RelX="0.0" RelY="0.7799999999999727" /> <Point X="279.0" Y="459.0" GraphRef="d9e59" RelX="0.9753086419753086" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1362408" /> </Interaction> <Interaction GraphId="da1a0"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="346.0" Y="428.0" GraphRef="eb488" RelX="0.0" RelY="0.7799999999999727" /> <Point X="348.0" Y="487.0" GraphRef="e2767" RelX="-0.003436426116838488" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1362408" /> </Interaction> <Interaction GraphId="dc61b"> <Comment Source="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.</Comment> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="149.0" Y="208.0" /> <Point X="221.0" Y="209.0" /> <Anchor Position="0.0" Shape="None" GraphId="dd910" /> <Anchor Position="0.99" Shape="None" GraphId="cf301" /> <Anchor Position="0.5" Shape="None" GraphId="df17d" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1362417" /> </Interaction> <Interaction GraphId="e1b18"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="349.0" Y="298.0" GraphRef="e2bef" RelX="0.0" RelY="0.9130434782608695" /> <Point X="344.0" Y="384.0" GraphRef="cbf21" RelX="-2.0" RelY="-5.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1362408" /> </Interaction> <Interaction GraphId="e1e46"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="417.0" Y="346.0" GraphRef="d9f5f" RelX="-1.0" RelY="0.0" /> <Point X="346.0" Y="350.0" GraphRef="bafc3" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1362408" /> </Interaction> <Interaction GraphId="e25e9"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="221.0" Y="209.0" GraphRef="cf301" RelX="0.7199999999999989" RelY="0.009999999999990905" /> <Point X="224.0" Y="211.0" GraphRef="e1813" RelX="-1.0" RelY="-0.034482758620689655" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-1362417" /> </Interaction> <Interaction GraphId="e322a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="628.0" Y="608.0" GraphRef="bf8a6" RelX="0.6299999999999955" RelY="-0.009999999999990905" /> <Point X="666.0" Y="570.0" GraphRef="a4637" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-8878815" /> </Interaction> <Interaction GraphId="e3c2d"> <Comment Source="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. 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xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="d8d"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">12785837</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Iron-sulfur cluster biosynthesis. Characterization of frataxin as an iron donor for assembly of [2Fe-2S] clusters in ISU-type proteins.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Yoon T, Cowan JA.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="c4e"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">1567230</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Expression and characterization of human mitochondrial ferredoxin reductase in Escherichia coli.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Brandt ME, Vickery LE.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="c21"> <bp:ID 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important for iron-sulfur cluster biogenesis.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Shi Y, Ghosh M, Kovtunovych G, Crooks DR, Rouault TA.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="ed5"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">12947415</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Gerber J, Mühlenhoff U, Lill R.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="be5"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">22511353</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">(IscS-IscU)2 complex structures provide insights into Fe2S2 biogenesis and transfer.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Marinoni EN, de Oliveira JS, Nicolet Y, Raulfs EC, Amara P, Dean DR, Fontecilla-Camps JC.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="d8e"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">21944046</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Mutations in iron-sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cameron JM, Janer A, Levandovskiy V, Mackay N, Rouault TA, Tong WH, Ogilvie I, Shoubridge EA, Robinson BH.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="f6a"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">20522547</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Frataxin and mitochondrial FeS cluster biogenesis.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Stemmler TL, Lesuisse E, Pain D, Dancis A.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="e0d"> <bp:ID 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rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Tong WH, Rouault T.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="d36"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">17331979</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Shan Y, Napoli E, Cortopassi G.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="aab"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">20873749</bp:ID> <bp:DB 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rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe/S cluster biosynthesis.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Sheftel AD, Stehling O, Pierik AJ, Elsässer HP, Mühlenhoff U, Webert H, Hobler A, Hannemann F, Bernhardt R, Lill R.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="fb6"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">22382365</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Biogenesis of iron-sulfur clusters in mammalian cells: new insights and relevance to human disease.</bp:TITLE> <bp:AUTHORS 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Nakai Y, Elsässer HP, Lill R.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="fff"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">18425540</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Mapping iron binding sites on human frataxin: implications for cluster assembly on the ISU Fe-S cluster scaffold protein.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Huang J, Dizin E, Cowan JA.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="fad"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">21987576</bp:ID> <bp:DB 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L.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="ad6"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">19675643</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Function and biogenesis of iron-sulphur proteins.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Lill R.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="b1b"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">15509595</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Iron-sulfur protein maturation in human cells: evidence for a function of frataxin.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Stehling O, Elsässer HP, Brückel B, Mühlenhoff U, Lill R.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="c39"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">26016518</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Frataxin Accelerates [2Fe-2S] Cluster Formation on the Human Fe-S Assembly Complex.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Fox NG, Das D, Chakrabarti M, Lindahl PA, Barondeau DP.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="aec"> <bp:ID 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xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="d3f"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">23906713</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">The role of mitochondria in cellular iron-sulfur protein biogenesis: mechanisms, connected processes, and diseases.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Stehling O, Lill R.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="cad"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">22077971</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">A fatal mitochondrial disease is associated with defective NFU1 function in the maturation of a subset of mitochondrial Fe-S proteins.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">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.</bp:AUTHORS> </bp:PublicationXref> <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#"> <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">classic metabolic pathway</bp:TERM> <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PW:0000002</bp:ID> <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Pathway Ontology</bp:Ontology> </bp:openControlledVocabulary> 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