Activation of the Iron Regulon by the Yeast Aft1/Aft2 Transcription Factors Depends on Mitochondrial but Not Cytosolic Iron-Sulfur Protein Biogenesis

Rutherford, Julian C., Ojeda, Luis, Balk, Janneke, Mühlenhoff, Ulrich, Lill, Roland and Winge, Dennis R. (2005) Activation of the Iron Regulon by the Yeast Aft1/Aft2 Transcription Factors Depends on Mitochondrial but Not Cytosolic Iron-Sulfur Protein Biogenesis. Journal of Biological Chemistry, 280 (11). pp. 10135-10140. ISSN 0021-9258

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Abstract

Two transcriptional activators, Aft1 and Aft2, regulate iron homeostasis in Saccharomyces cerevisiae. These factors induce the expression of iron regulon genes in iron-deficient yeast but are inactivated in iron-replete cells. Iron inhibition of Aft1/Aft2 is abrogated in cells defective for Fe-S cluster biogenesis within the mitochondrial matrix (Chen, O. S., Crisp, R. J., Valachovic, M., Bard, M., Winge, D. R., and Kaplan, J. (2004) J. Biol. Chem. 279, 29513–29518). To determine whether iron sensing by Aft1/Aft2 requires the function of the mitochondrial Fe-S export and cytosolic Fe-S protein assembly systems, we evaluated the expression of the iron regulon in cells depleted of glutathione and in cells depleted of Atm1, Nar1, Cfd1, and Nbp35. The iron regulon is induced in cells depleted of Atm1 with Aft1 largely responsible for the induced gene expression. Aft2 is activated at a later time in Atm1-depleted cells. Likewise, the iron regulon is induced in cells depleted of glutathione. In contrast, repression of NAR1, CFD1, or NBP35 fails to induce the iron regulon despite strong inhibition of cytosolic/nuclear Fe-S protein assembly. Thus, iron sensing by Aft1/Aft2 is not linked to the maturation of cytosolic/nuclear Fe-S proteins, but the mitochondrial inner membrane transporter Atm1 is important to transport the inhibitory signal. Although Aft1 and Aft2 sense a signal emanating from the Fe-S cluster biogenesis pathway, there is no indication that the proteins are inhibited by direct binding of an Fe-S cluster.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Molecular Microbiology Faculty of Science > Research Groups > Plant Sciences
Depositing User:	Rhiannon Harvey
Date Deposited:	07 Feb 2012 14:51
Last Modified:	24 Oct 2022 02:11
URI:	https://ueaeprints.uea.ac.uk/id/eprint/36906
DOI:	10.1074/jbc.M413731200

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