The glucose sensor Snf1 and the transcription factors Msn2 and Msn4 regulate transcription of the vacuolar iron importer gene and iron resistance in yeast.

The budding yeast stores iron in the vacuole, which is a major resistance mechanism against iron toxicity. One key protein involved in vacuolar iron storage is the iron importer Ccc1, which facilitates iron entry into the vacuole. Transcription of the gene is largely regulated by the binding of iron-sulfur clusters to the activator domain of the transcriptional activator Yap5. Additional evidence, however, suggests that Yap5-independent transcriptional activation of also contributes to iron resistance. Here, we demonstrate that components of the signaling pathway involving the low-glucose sensor Snf1 regulate transcription and iron resistance. We found that deletion acts synergistically with deletion to regulate transcription and iron resistance. A kinase-dead mutation of Snf1 lowered iron resistance as did deletion of , which encodes a partner protein of Snf1. Deletion of all three alternative partners of Snf1 encoded by , , and decreased both transcription and iron resistance. The Snf1 complex is known to activate the general stress transcription factors Msn2 and Msn4. We show that Msn2 and Msn4 contribute to Snf1-mediated transcription. Of note, deletion in combination with and deletion resulted in additive effects on transcription, suggesting that other activators contribute to the regulation of transcription. In conclusion, we show that yeast have developed multiple transcriptional mechanisms to regulate Ccc1 expression and to protect against high cytosolic iron toxicity.