title: Ascorbic acid enhances ferritin mRNA translation by an IRP/aconitase switch.
abstract: Replenishment of ascorbate in cultured cells, which are almost uniformly vitamin-deficient, increases ferritin mRNA translation in response to iron by 20-fold (Toth, I., Rogers, J. T., McPhee, J. A., Elliott, S. M., Abramson, S. L., and Bridges, K. R. (1995) J. Biol. Chem. 270, 2846-2852). We now demonstrate that ascorbate increases cytosolic aconitase activity. The iron-responsive element-binding protein (IRP-1) exists in three states: bound to mRNA without aconitase activity, free in the cytosol without aconitase activity, and free in the cytosol with aconitase activity. Ascorbate converts free IRP-1 to the enzymatically active form. Enhanced ferritin synthesis with subsequent iron stimulation is due to the altered equilibrium of the free IRP-1. The cellular biology of iron is closely intertwined with that of ascorbate.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: I
authors.initials: I
authors.lastname: Toth
authors.forename: K R
authors.initials: KR
authors.lastname: Bridges
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology; D005293:Ferritins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D035941:Iron Regulatory Protein 1; D035925:Iron-Regulatory Proteins; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000975:Antioxidants; D035925:Iron-Regulatory Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D005293:Ferritins; D000154:Aconitate Hydratase; D035941:Iron Regulatory Protein 1; D001205:Ascorbic Acid