Friedreich ataxia: a paradigm for mitochondrial diseases

Curr Opin Genet Dev. 2002 Jun;12(3):272-7. doi: 10.1016/s0959-437x(02)00298-8.

Abstract

Friedreich ataxia (FRDA), a progressive neurodegenerative disease, is due to the partial loss of function of frataxin, a mitochondrial protein of unknown function. Loss of frataxin causes mitochondrial iron accumulation, deficiency in the activities of iron-sulfur (Fe-S) proteins, and increased oxidative stress. Mouse models for FRDA demonstrate that the Fe-S deficit precedes iron accumulation, suggesting that iron accumulation is a secondary event. Furthermore, increased oxidative stress in FRDA patients has been demonstrated, and in vitro experiments imply that the frataxin defect impairs early antioxidant defenses. These results taken together suggest that frataxin may function either in mitochondrial iron homeostasis, in Fe-S cluster biogenesis, or directly in the response to oxidative stress. It is clear, however, that the pathogenic mechanism in FRDA involves free-radical production and oxidative stress, a process that appears to be sensitive to antioxidant therapies.

Publication types

  • Review

MeSH terms

  • Animals
  • Friedreich Ataxia / genetics*
  • Friedreich Ataxia / therapy
  • Homeostasis
  • Humans
  • Iron / metabolism
  • Iron-Binding Proteins / genetics
  • Iron-Binding Proteins / physiology
  • Iron-Sulfur Proteins / biosynthesis
  • Mice
  • Mitochondria / genetics*
  • Oxidative Stress / physiology

Substances

  • Iron-Binding Proteins
  • Iron-Sulfur Proteins
  • frataxin
  • Iron