Mammalian frataxin: an essential function for cellular viability through an interaction with a preformed ISCU/NFS1/ISD11 iron-sulfur assembly complex

PLoS One. 2011 Jan 26;6(1):e16199. doi: 10.1371/journal.pone.0016199.


Background: Frataxin, the mitochondrial protein deficient in Friedreich ataxia, a rare autosomal recessive neurodegenerative disorder, is thought to be involved in multiple iron-dependent mitochondrial pathways. In particular, frataxin plays an important role in the formation of iron-sulfur (Fe-S) clusters biogenesis.

Methodology/principal findings: We present data providing new insights into the interactions of mammalian frataxin with the Fe-S assembly complex by combining in vitro and in vivo approaches. Through immunoprecipitation experiments, we show that the main endogenous interactors of a recombinant mature human frataxin are ISCU, NFS1 and ISD11, the components of the core Fe-S assembly complex. Furthermore, using a heterologous expression system, we demonstrate that mammalian frataxin interacts with the preformed core complex, rather than with the individual components. The quaternary complex can be isolated in a stable form and has a molecular mass of ≈190 kDa. Finally, we demonstrate that the mature human FXN(81-210) form of frataxin is the essential functional form in vivo.

Conclusions/significance: Our results suggest that the interaction of frataxin with the core ISCU/NFS1/ISD11 complex most likely defines the essential function of frataxin. Our results provide new elements important for further understanding the early steps of de novo Fe-S cluster biosynthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon-Sulfur Lyases / metabolism
  • Cell Survival*
  • Humans
  • Iron-Binding Proteins / physiology*
  • Iron-Regulatory Proteins / metabolism
  • Iron-Sulfur Proteins / metabolism*
  • Mitochondrial Proteins
  • Multiprotein Complexes / biosynthesis
  • Multiprotein Complexes / metabolism*
  • Protein Binding


  • ISCU protein, human
  • Iron-Binding Proteins
  • Iron-Regulatory Proteins
  • Iron-Sulfur Proteins
  • LYRM4 protein, human
  • Mitochondrial Proteins
  • Multiprotein Complexes
  • frataxin
  • Carbon-Sulfur Lyases
  • NFS1 protein, human