title: Disabled early recruitment of antioxidant defenses in Friedreich's ataxia.
abstract: Friedreich's ataxia (FRDA) results from a generalized deficiency of mitochondrial iron-sulfur protein activity ascribed to mitochondrial iron overload. However, iron overload appears to be a late event in the disease. Here we show that neither superoxide dismutases nor the import iron machinery was induced by an endogenous oxidative stress in FRDA patients' fibroblasts in contrast to control cells. Superoxide dismutase activity was not induced in the heart of conditional frataxin-KO mice either. This suggests that continuous oxidative damage to iron-sulfur clusters, resulting from hampered superoxide dismutase signaling, is causative of the mitochondrial deficiency and long term mitochondrial iron overload occurring in FRDA.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Tour Lavoisier, Hôpital Necker-Enfants-Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France.
authors.forename: K
authors.initials: K
authors.lastname: Chantrel-Groussard
authors.forename: V
authors.initials: V
authors.lastname: Geromel
authors.forename: H
authors.initials: H
authors.lastname: Puccio
authors.forename: M
authors.initials: M
authors.lastname: Koenig
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: A
authors.initials: A
authors.lastname: Rötig
authors.forename: P
authors.initials: P
authors.lastname: Rustin
mesh_terms: D000328:Adult; D000818:Animals; D001706:Biopsy; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology; D005621:Friedreich Ataxia / Q000201:enzymology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D033862:Iron-Binding Proteins; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009840:Oligomycins / Q000494:pharmacology; D018384:Oxidative Stress; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000378:metabolism*; D000096923:Frataxin
chemical_list: D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D007501:Iron; D033862:Iron-Binding Proteins; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D009840:Oligomycins; D017853:Phosphotransferases (Alcohol Group Acceptor); D016601:RNA-Binding Proteins; D011990:Receptors, Transferrin; D013482:Superoxide Dismutase; D000096923:Frataxin