Bacterial frataxin CyaY is the gatekeeper of iron-sulfur cluster formation catalyzed by IscS

Nat Struct Mol Biol. 2009 Apr;16(4):390-6. doi: 10.1038/nsmb.1579. Epub 2009 Mar 22.


Frataxin is an essential mitochondrial protein whose reduced expression causes Friedreich's ataxia (FRDA), a lethal neurodegenerative disease. It is believed that frataxin is an iron chaperone that participates in iron metabolism. We have tested this hypothesis using the bacterial frataxin ortholog, CyaY, and different biochemical and biophysical techniques. We observe that CyaY participates in iron-sulfur (Fe-S) cluster assembly as an iron-dependent inhibitor of cluster formation, through binding to the desulfurase IscS. The interaction with IscS involves the iron binding surface of CyaY, which is conserved throughout the frataxin family. We propose that frataxins are iron sensors that act as regulators of Fe-S cluster formation to fine-tune the quantity of Fe-S cluster formed to the concentration of the available acceptors. Our observations provide new perspectives for understanding FRDA and a mechanistic model that rationalizes the available knowledge on frataxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism*
  • Carbon-Sulfur Lyases / metabolism*
  • Chromatography, Gel
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins
  • Iron / metabolism*
  • Iron-Binding Proteins / metabolism*
  • Kinetics
  • Macromolecular Substances / metabolism
  • Models, Molecular
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping


  • Bacterial Proteins
  • CyaY protein, E coli
  • Escherichia coli Proteins
  • Iron-Binding Proteins
  • Macromolecular Substances
  • Iron
  • Carbon-Sulfur Lyases
  • cysteine desulfurase