Disabled early recruitment of antioxidant defenses in Friedreich's ataxia

Friedreich's ataxia (FRDA) results from a generalized deficiency of mitocho ndrial 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 conti nuous oxidative damage to iron-ulfur clusters, resulting from hampered supe roxide dismutase signaling, is causative of the mitochondrial deficiency an d long term mitochondrial iron overload occurring in FRDA.