title: A role for IOP1 in mammalian cytosolic iron-sulfur protein biogenesis.
abstract: The biogenesis of cytosolic iron-sulfur (Fe-S) proteins in mammalian cells is poorly understood. In Saccharomyces cerevisiae, there is a pathway dedicated to cytosolic Fe-S protein maturation that involves several essential proteins. One of these is Nar1, which intriguingly is homologous to iron-only hydrogenases, ancient enzymes that catalyze the formation of hydrogen gas in anaerobic bacteria. There are two orthologues of Nar1 in mammalian cells, iron-only hydrogenase-like protein 1 (IOP1) and IOP2 (also known as nuclear prelamin A recognition factor). We examined IOP1 for a potential role in mammalian cytosolic Fe-S protein biogenesis. We found that knockdown of IOP1 in both HeLa and Hep3B cells decreases the activity of cytosolic aconitase, an Fe-S protein, but not that of mitochondrial aconitase. Knockdown of IOP2, in contrast, had no effect on either. The decrease in aconitase activity upon IOP1 knockdown is rescued by expression of a small interference RNA-resistant version of IOP1. Upon loss of its Fe-S cluster, cytosolic aconitase is known to be converted to iron regulatory protein 1, and consistent with this, we found that IOP1 knockdown increases transferrin receptor 1 mRNA levels and decreases ferritin heavy chain protein levels. IOP1 knockdown also leads to a decrease in activity of xanthine oxidase, a distinct cytosolic Fe-S protein. Taken together, these results provide evidence that IOP1 is involved in mammalian cytosolic Fe-S protein maturation.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Daisheng
authors.initials: D
authors.lastname: Song
authors.forename: Frank S
authors.initials: FS
authors.lastname: Lee
mesh_terms: D000154:Aconitate Hydratase / Q000096:biosynthesis / Q000235:genetics; D001052:Apoferritins / Q000096:biosynthesis / Q000235:genetics; D001421:Bacteria, Anaerobic / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D006864:Hydrogenase / Q000235:genetics / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D035941:Iron Regulatory Protein 1 / Q000096:biosynthesis / Q000235:genetics; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism; D008667:Metalloproteins / Q000096:biosynthesis* / Q000235:genetics; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013455:Sulfur / Q000378:metabolism; D014969:Xanthine Oxidase / Q000096:biosynthesis / Q000235:genetics
chemical_list: C516542:CIAO3 protein, human; D007506:Iron-Sulfur Proteins; D008667:Metalloproteins; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D029701:Saccharomyces cerevisiae Proteins; D013455:Sulfur; D001052:Apoferritins; D007501:Iron; D006864:Hydrogenase; C501975:Nar1 protein, S cerevisiae; D014969:Xanthine Oxidase; D000154:Aconitate Hydratase; D035941:Iron Regulatory Protein 1