The mitochondrial iron exporter genes and in yeast are transcriptionally regulated by Aft1 and Yap1.

Budding yeast () responds to low cytosolic iron by up-regulating the expression of iron import genes; iron import can reflect iron transport into the cytosol or mitochondria. Mmt1 and Mmt2 are nuclearly encoded mitochondrial proteins that export iron from the mitochondria into the cytosol. Here we report that and expression is transcriptionally regulated by two pathways: the low-iron-sensing transcription factor Aft1 and the oxidant-sensing transcription factor Yap1. We determined that and expression is increased under low-iron conditions and decreased when mitochondrial iron import is increased through overexpression of the high-affinity mitochondrial iron importer Mrs3. Moreover, loss of iron-sulfur cluster synthesis induced expression of and We show that exposure to the oxidant HO induced expression but not expression and identified the transcription factor Yap1 as being involved in oxidant-mediated expression. We defined Aft1- and Yap1-dependent transcriptional sites in the promoter that are necessary for low-iron- or oxidant-mediated expression. We also found that the promoter contains domains that are important for regulating its expression under low-iron conditions, including an upstream region that appears to partially repress expression under low-iron conditions. Our findings reveal that and are induced under low-iron conditions and that the low-iron regulator Aft1 is required for this induction. We further uncover an Aft1-binding site in the promoter sufficient for inducing transcription and identify an promoter region required for low iron induction.