Frataxin: a protein in search for a function

J Neurochem. 2013 Aug:126 Suppl 1:43-52. doi: 10.1111/jnc.12220.

Abstract

Reduced levels of the protein frataxin cause the neurodegenerative disease Friedreich's ataxia. Pathology is associated with disruption of iron-sulfur cluster biosynthesis, mitochondrial iron overload, and oxidative stress. Frataxin is a highly conserved iron-binding protein present in most organisms. Despite the intense interest generated since the determination of its pathology, identification of the cellular function of frataxin has so far remained elusive. In this review, we revisit the most significant milestones that have led us to our current understanding of frataxin and its functions. The picture that emerges is that frataxin is a crucial element of one of the most essential cellular machines specialized in iron-sulfur cluster biogenesis. Future developments, therefore, can be expected from further advancements in our comprehension of this machine.

Keywords: Friedreich's ataxia; iron metabolism; mitochondria; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Frataxin
  • Humans
  • Iron / metabolism
  • Iron-Binding Proteins / chemistry
  • Iron-Binding Proteins / genetics
  • Iron-Binding Proteins / metabolism
  • Iron-Binding Proteins / physiology*
  • Mitochondria / metabolism
  • Molecular Chaperones / metabolism
  • Molecular Sequence Data
  • Mutation / genetics
  • Mutation / physiology
  • Protein Conformation
  • Sulfur / metabolism

Substances

  • Iron-Binding Proteins
  • Molecular Chaperones
  • Sulfur
  • Iron