Recent advances in the molecular pathogenesis of Friedreich ataxia.

Abstract

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.

• Authors: H Puccio, M Koenig
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 9 Issue 6 Pg. 887-92 (Apr 12 2000) ISSN: 0964-6906 [Print] England
• PMID: 10767311 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Iron-Binding Proteins
• Iron-Sulfur Proteins
• Iron
• Phosphotransferases (Alcohol Group Acceptor)

Topics

• Friedreich Ataxia (genetics, therapy)
• Humans
• Iron (metabolism)
• Iron-Binding Proteins
• Iron-Sulfur Proteins (deficiency)
• Mitochondria (metabolism)
• Mutation
• Phosphotransferases (Alcohol Group Acceptor) (genetics)
• Frataxin