Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes

Friedreich ataxia is a progressive neurodegenerative disorder caused byloss of function mutations in the frataxin gene. In order to unravelfrataxin function we developed monoclonal antibodies raised againstdifferent regions of the protein. These antibodies detect a processed 18kDa protein in various human and mouse tissues and cell lines that isseverely reduced in Friedreich ataxia patients. By immunocytofluorescenceand immunocytoelectron microscopy we show that frataxin is located inmitochondria, associated with the mitochondrial membranes and crests.Analysis of cellular localization of various truncated forms of frataxinexpressed in cultured cells and evidence of removal of an N-terminalepitope during protein maturation demonstrated that the mitochondrialtargetting sequence is encoded by the first 20 amino acids. Given theshared clinical features between Friedreich ataxia, vitamin E deficiencyand some mitochondriopathies, our data suggest that a reduction in frataxinresults in oxidative damage.