Recent advances in the molecular pathogenesis of Friedreich ataxia.
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 patient heart autopsies have shown that frataxin defect causes mitochondrial iron accumulation. Biochemical data from patient 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 radical production and oxidative stress, a process that might be sensitive to antioxidant therapies.
Puccio
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H
Institut de Génètique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP), 1 rue Laurent Fries BP163, 67404 Illkirch, CU de Strasbourg, France.
Koenig
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M
D005621:Friedreich Ataxia / Q000235:genetics* / Q000628:therapy; D006801:Humans; D007501:Iron / Q000378:metabolism; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins / Q000172:deficiency; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D000096923:Frataxin
D007501:Iron; D033862:Iron-Binding Proteins; D007506:Iron-Sulfur Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D000096923:Frataxin