title: Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and maturation of different subsets of cytosolic-nuclear iron-sulfur proteins.
abstract: Numerous cytosolic and nuclear proteins involved in metabolism, DNA maintenance, protein translation, or iron homeostasis depend on iron-sulfur (Fe/S) cofactors, yet their assembly is poorly defined. Here, we identify and characterize human CIA2A (FAM96A), CIA2B (FAM96B), and CIA1 (CIAO1) as components of the cytosolic Fe/S protein assembly (CIA) machinery. CIA1 associates with either CIA2A or CIA2B and the CIA-targeting factor MMS19. The CIA2B-CIA1-MMS19 complex binds to and facilitates assembly of most cytosolic-nuclear Fe/S proteins. In contrast, CIA2A specifically matures iron regulatory protein 1 (IRP1), which is critical for cellular iron homeostasis. Surprisingly, a second layer of iron regulation involves the stabilization of IRP2 by CIA2A binding or upon depletion of CIA2B or MMS19, even though IRP2 lacks an Fe/S cluster. In summary, CIA2B-CIA1-MMS19 and CIA2A-CIA1 assist different branches of Fe/S protein assembly and intimately link this process to cellular iron regulation via IRP1 Fe/S cluster maturation and IRP2 stabilization.
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Strasse, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stehling
authors.forename: Judita
authors.initials: J
authors.lastname: Mascarenhas
authors.forename: Ajay A
authors.initials: AA
authors.lastname: Vashisht
authors.forename: Alex D
authors.initials: AD
authors.lastname: Sheftel
authors.forename: Brigitte
authors.initials: B
authors.lastname: Niggemeyer
authors.forename: Ralf
authors.initials: R
authors.lastname: Rösser
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Pierik
authors.forename: James A
authors.initials: JA
authors.lastname: Wohlschlegel
authors.forename: Roland
authors.initials: R
authors.lastname: Lill
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D035941:Iron Regulatory Protein 1 / Q000378:metabolism; D035942:Iron Regulatory Protein 2 / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000096:biosynthesis* / Q000378:metabolism; D056511:Metallochaperones / Q000235:genetics / Q000378:metabolism*; D008667:Metalloproteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C112111:CIAO1 protein, human; C574944:CIAO2A protein, human; C569498:CIAO2B protein, human; D002352:Carrier Proteins; D007506:Iron-Sulfur Proteins; C416322:MMS19 protein, human; D056511:Metallochaperones; D008667:Metalloproteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D007501:Iron; D005992:Glycerol-3-Phosphate O-Acyltransferase; C546175:ACO1 protein, human; C546174:IREB2 protein, human; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2
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