Iron-sulfur cluster biogenesis and human disease

Trends Genet. 2008 Aug;24(8):398-407. doi: 10.1016/j.tig.2008.05.008. Epub 2008 Jul 5.


Iron-sulfur (Fe-S) clusters are essential for numerous biological processes, including mitochondrial respiratory chain activity and various other enzymatic and regulatory functions. Human Fe-S cluster assembly proteins are frequently encoded by single genes, and inherited defects in some of these genes cause disease. Recently, the spectrum of diseases attributable to abnormal Fe-S cluster biogenesis has extended beyond Friedreich ataxia to include a sideroblastic anemia with deficiency of glutaredoxin 5 and a myopathy associated with a deficiency of a Fe-S cluster assembly scaffold protein, ISCU. Mutations within other mammalian Fe-S cluster assembly genes could be causative for human diseases that manifest distinctive combinations of tissue-specific impairments. Thus, defects in the iron-sulfur cluster biogenesis pathway could underlie many human diseases.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Anemia, Sideroblastic / genetics
  • Friedreich Ataxia / genetics
  • Glutaredoxins / genetics
  • Humans
  • Iron-Binding Proteins / genetics
  • Iron-Sulfur Proteins / biosynthesis*
  • Iron-Sulfur Proteins / genetics*
  • Models, Biological
  • Muscular Diseases / genetics
  • Mutation


  • ABCB7 protein, human
  • ATP-Binding Cassette Transporters
  • GLRX5 protein, human
  • Glutaredoxins
  • ISCU protein, human
  • Iron-Binding Proteins
  • Iron-Sulfur Proteins
  • frataxin