Transcription of the Yeast Iron Regulon Does Not Respond Directly to Iron but Rather to Iron-Sulfur Cluster Biosynthesis

We demonstrate that transcription of these genes does not respond directly to cytosolic iron but rather to the mitochondrial utilization of iron for the synthesis of iron-sulfur clusters

Opal S. Chen; Robert J. Crisp; Martin Valachovic; Martin Bard; Dennis R. Winge; Jerry Kaplan

2004

Scholarcy highlights

  • High affinity iron uptake in Saccharomyces cerevisiae is mediated by a transport system comprising the multicopper oxidase Fet3p and the transmembrane permease Ftr1p
  • We showed that disruption of mitochondrial Fe-S biosynthesis, which results in excessive mitochondrial iron accumulation, leads to transcription of the iron transport system independent of the cytosolic iron level
  • Decreased Cytosolic Iron Levels Induce the Iron Regulon—We developed a system in which we could determine the effect of cytosolic iron on induction of the iron transport system
  • Our data strongly suggest that Aft1p may not directly sense elemental iron but rather senses Fe-S clusters or a signal arising from an Fe-S-containing enzyme
  • This conclusion is based on the observation that induction of the iron regulon by the inhibition of Fe-S cluster synthesis occurs when cytosolic iron levels are high
  • Reduction in cytosolic iron led to decreased growth as a consequence of decreased ergosterol biosynthesis
  • We utilized the erg25-2 allele to show that reduction in Fe-S cluster synthesis, which induces transcription of the iron regulon, does not lead to a reduction in cytosolic iron; the sterol profile of the erg25-2 cell appeared normal

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