Hemin rescues adrenodoxin, heme a and cytochrome oxidase activity in frataxin-deficient oligodendroglioma cells

Eleonora Napoli, Dexter Morin, Rita Bernhardt, Alan R Buckpitt, Gino A Cortopassi

Research output: Contribution to journalArticle

29 Scopus citations


Mutations in the frataxin gene cause neurodegeneration and demyelination in Friedreich's ataxia. We showed earlier that frataxin deficiency causes primary iron-sulfur cluster defects, and later causes defects in heme and cytochrome c hemoprotein levels. Iron-sulfur (Fe/S) clusters are required in two enzymes of heme biosynthesis in humans i.e. in ferrochelatase and adrenodoxin. However, decreases in ferrochelatase activity have not been observed in frataxin-deficient HeLa cells or patient lymphoblasts. We knocked down frataxin in oligodendroglioma cells using siRNA, which produced significant defects in the activity of the Fe/S cluster enzymes adrenodoxin and aconitase, the adrenodoxin product heme a, and cytochrome oxidase, for which heme a serves as a prosthetic group. Exogenous hemin produced a significant rescue of adrenodoxin, aconitase, heme a levels and cytochrome oxidase activity. Thus hemin rescues iron-sulfur cluster defects that are the result of frataxin-deficiency, perhaps as a consequence of increasing the pool of bioavailable iron, and thus should be more fully tested for beneficial effects in Friedreich's ataxia models.

Original languageEnglish (US)
Pages (from-to)773-780
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Issue number7
StatePublished - Jul 2007



  • Adrenodoxin
  • Frataxin
  • Heme
  • Hemin
  • Iron-sulfur cluster
  • RNAi
  • Theraphy

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics

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