STUDIES OF HUMAN, MOUSE AND YEAST HOMOLOGS INDICATE A MITOCHONDRIAL-FUNCTION FOR FRATAXIN

Friedreich's ataxia is due to loss of function mutations in the gene e ncoding frataxin (FRDA). Frataxin is a protein of unknown function. In situ hybridization analyses revealed that mouse frataxin expression c orrelates well with the main site of neurodegeneration, but the expres sion pattern is broader than expected from the pathology of the diseas e. Frataxin mRNA is predominantly expressed in tissues with a high met abolic rate, including liver, kidney, brown fat and heart. We found th at mouse and yeast frataxin homologues contain a potential mitochondri al targeting sequence in their N-terminal domains and that disruption of the yeast gene results in mitochondrial dysfunction. Finally, taggi ng experiments demonstrate that human frataxin co-localizes with a mit ochondrial protein. Friedreich's ataxia is therefore a mitochondrial d isease caused by a mutation in the nuclear genome.