SCAN:Strategies used by yeast to overcome iron overload

ITQB Scan Seminar

Title: Strategies used by yeast to overcome iron overload

From: Genomics and Stress Laboratory

Abstract: 

Disruption of iron homeostasis originates significant damage in cells. Organisms have evolved sophisticated mechanisms that, on one hand avoid the drastic consequences of iron scarcity and, on the other hand circumvent the toxic effects of iron overload.  The budding yeast Saccharomyces cerevisiae is able to grow under a wide magnitude of Fe accessible environments and can survive large fluctuations in Fe bioavailability. Therefore, S. cerevisiae is an attractive organism for studies in iron homeostasis as it is genetically amenable, easily manipulated and represents a simple working model for teasing away the complexity of higher eukaryotic cells.
Unlike vertebrates, but similar to plants, the yeast cell vacuoles function as iron reservoirs. Ccc1 is the vacuolar transporter that mediates iron storage in yeast. In a high-Fe milieu, CCC1 deletion is lethal and Yap5 - one of the eight members of the Yap Activator Protein (Yap) family - regulates its expression. 
In this work we show that besides the iron vacuolar transporter CCC1, Yap5 also directly controls the expression of glutaredoxin GRX4, previously known to be involved in the regulation of the nuclear localization of Aft1 (the major transcriptional activator in Fe deficiency). Consistently, we show that in the absence of Yap5, Aft1 nuclear exclusion is slightly impaired.
In addition we demonstrate that Yap5-mediated regulation of CCC1 is not essential for cells to overcome iron overload. This new finding brings forward the hypothesis that another yet unidentified factor is regulating iron storage in yeast.  This hypothesis is further corroborated by the unexpected observation that Yap5 is degraded in the presence of iron. Interestingly, the removal of CCC1 3’ untranslated region (3’UTR) renders yeast cells more sensitive to growth under Fe overload, strongly suggesting that CCC1 is also posttranscriptionally regulated.
Overall, this work provides further evidence that cells avoid iron overload by using multiple pathways.