Résumé
Friedreich ataxia, the most frequent cause of recessive ataxia is due in most cases to a homozygous intronic expansion resulting in the loss of function of frataxin. Frataxin is a mitochondrial protein conserved through evolution. Yeast knock-out models and histological data from patients heart autopsies have shown that frataxin defect causes mitochondrial iron accumulation. Biochemical data from patients heart biopsies or autopsies have revealed a specific deficiency in the activities of aconitases and of mitochondrial iron–sulfur proteins. These results suggest that frataxin may play a role either in mitochondrial iron transport or in iron–sulfur cluster assembly or transport. Iron abnormalities suggest a pathogenic mechanism involving free radicals production and oxidative stress, a process that might be sensitive to anti-oxidant therapies.