Deciphering the cause of Friedreich ataxia

Abstract

Friedreich ataxia (FA), the most frequent cause of recessive ataxia, is attributable, in most cases, to a large expansion of an intronic GAA repeat, resulting in decreased expression of the target frataxin gene. This gene encodes a novel mitochondrial protein that has homologues of unknown function in yeast and even in gram-negative bacteria. Yeast deficient in the frataxin homologue accumulate iron in their mitochondria and show increased sensitivity to oxidative stress. This finding suggests that FA patients suffer from a mitochondrial dysfunction that causes free-radical toxicity, reminiscent of the clinically similar ataxia caused by inherited isolated vitamin E deficiency.