Yap5-regulated transcription of TYW1 protects yeast from high iron toxicity.

The budding yeast Saccharomyces cerevisiae responds to high cytosolic iron by inducing Yap5-mediated transcription. We identified genes regulated by Yap5 in response to iron and show that one of the genes induced is TYW1, which encodes an iron-sulfur cluster enzyme that participates in the synthesis of Wybutosine (yW) modified t-RNA. ...
Strains deleted for TYW1 do not show a phenotype in standard yeast medium. In contrast, overexpression of TYW1 results in decreased cell growth and induction of the iron regulon leading to increased expression of the high affinity iron transporters. We identified a minimal domain of S. cerevisiae Tyw1 that is sufficient to induce the iron regulon. CCC1, a vacuolar iron importer, is a Yap5-regulated gene and deletion of either CCC1 or YAP5 results in high iron sensitivity. Deletion of TYW1 in a ccc1 strain leads to increased iron sensitivity. The increased iron sensitivity of ccc1tyw1 can be suppressed by overexpression of iron-sulfur cluster enzymes. We conclude that the Yap5-mediated induction of TYW1 provides protection from high iron toxicity by the consumption of free cytosolic iron through the formation of protein bound iron-sulfur clusters.
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Date: Sep. 14, 2011
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