Disabled early recruitment of antioxidant defenses in Friedreich's ataxia

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...

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Bibliographic Details
Published in:Human molecular genetics 2001-09, Vol.10 (19), p.2061-2067
Main Authors: CHANTREL-GROUSSARD, Karine, GEROMEL, Vanna, PUCCIO, Hélène, KOENIG, Michel, MUNNICH, Arnold, RÖTIG, Agnès, RUSTIN, Pierre
Format: Article
Language:English
Subjects:
Adult
Animals
Biochemistry, Molecular Biology
Biological and medical sciences
Biopsy
Cells, Cultured
Cytochrome c Group - metabolism
Enzyme Inhibitors - pharmacology
Fibroblasts - enzymology
Frataxin
Friedreich Ataxia - enzymology
Fundamental and applied biological sciences. Psychology
Humans
Iron - metabolism
Iron-Binding Proteins
Iron-Regulatory Proteins
Iron-Sulfur Proteins - metabolism
Life Sciences
Mice
Mice, Knockout
Molecular and cellular biology
Oligomycins - pharmacology
Oxidative Stress
Phosphotransferases (Alcohol Group Acceptor) - genetics
Receptors, Transferrin - metabolism
RNA-Binding Proteins - metabolism
Skin - drug effects
Skin - enzymology
Superoxide Dismutase - metabolism
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Summary: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.
ISSN:0964-6906
1460-2083
1460-2083
DOI:10.1093/hmg/10.19.2061