The phylogenetic distribution of frataxin indicates a role in iron-sulfur cluster protein assembly

Martijn A. Huynen, Berend Snel, Peer Bork, Toby J. Gibson

Research output: Contribution to journalArticleAcademicpeer-review


Much has been learned about the cellular pathology of Friedreich's ataxia, a recessive neurodegenerative disease resulting from insufficient expression of the mitochondrial protein frataxin. However, the biochemical function of frataxin has remained obscure, hampering attempts at therapeutic intervention. To predict functional interactions of frataxin with other proteins we investigated whether its gene specifically co-occurs with any other genes in sequenced genomes. In 56 available genomes we identified two genomes with identical phylogenetic distributions to the frataxin/cyaY gene: hscA and hscB/JAC1. These genes have not only emerged in the same evolutionary lineage as the frataxin gene, they have also been lost at least twice with it, and they have been horizontally transferred with it in the evolution of the mitochondria. The proteins encoded by hscA and hscB, the chaperone HSP66 and the co-chaperone HSP20, have been shown to be required for the synthesis of 2Fe-2S clusters on ferredoxin in proteobacteria. JAC1, an ortholog of hscB, and SSQ1, a paralog of hscA, have been shown to be required for iron-sulfur cluster assembly in mitochondria of Saccharomyces cerevisiae. Combining data on the co-occurrence of genes in genomes with experimental and predicted cellular localization data of their proteins supports the hypothesis that frataxin is directly involved in iron-sulfur cluster protein assembly. They indicate that frataxin is specifically involved in the same sub-process as HSP20/Jac1p.
Original languageEnglish
Pages (from-to)2463-2468
Number of pages6
JournalHuman Molecular Genetics
Issue number21
Publication statusPublished - 1 Nov 2001


  • chaperone
  • ferredoxin
  • frataxin
  • heat shock protein
  • heat shock protein 20
  • heat shock protein 66
  • hscA protein
  • hscB protein
  • iron
  • Jac1 protein
  • SSQ1 protein
  • sulfur
  • unclassified drug
  • article
  • autosomal recessive disorder
  • biochemistry
  • cellular distribution
  • controlled study
  • cytopathology
  • degenerative disease
  • Friedreich ataxia
  • gene transfer
  • Gram negative bacterium
  • hypothesis
  • mitochondrion
  • molecular evolution
  • nonhuman
  • phylogeny
  • prediction
  • priority journal
  • protein assembly
  • protein expression
  • protein protein interaction
  • Saccharomyces cerevisiae


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