title: Increased IRP1 activity in Friedreich ataxia.
abstract: In low-iron conditions, the cytosolic iron-regulatory protein IRP1 binds to iron-responsive elements (IREs) in mRNAs encoding iron-regulated proteins. In high-iron conditions, IRP1 incorporates an iron-sulfur cluster (ISC), which interferes with IRE binding and prevents intracellular iron accumulation. Here we demonstrate an incomplete shift of IRP1 to its ISC form in Friedreich ataxia (FRDA) fibroblasts, associated with decreased activities of ISC respiratory complexes. Our data suggest an impaired adaptive response to iron accumulation in FRDA cells.
authors.affiliation: University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine, Room 509A, Stellar-Chance Laboratories, 422 Curie Blvd., Philadelphia, PA 19104, USA.
authors.forename: Lioba
authors.initials: L
authors.lastname: Lobmayr
authors.forename: David G
authors.initials: DG
authors.lastname: Brooks
authors.forename: Robert B
authors.initials: RB
authors.lastname: Wilson
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005347:Fibroblasts / Q000378:metabolism; D005621:Friedreich Ataxia / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007501:Iron / Q000494:pharmacology; D035941:Iron Regulatory Protein 1 / Q000378:metabolism*; D035925:Iron-Regulatory Proteins / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects
chemical_list: D035925:Iron-Regulatory Proteins; D007501:Iron; D042963:Electron Transport Complex II; D035941:Iron Regulatory Protein 1; D042967:Electron Transport Complex I