IMYA (International Meeting on Yeast Apoptosis) edition:10 location:Gothenburg, Sweden date:14 - 18 May 2014
The Saccharomyces cerevisiae protein kinase Sch9 has been demonstrated to be an in vitro and in vivo effector of sphingolipid signalling. In this study, the link between Sch9 and sphingolipid metabolism in S. cerevisiae was examined in vivo based on the observation that the sch9Δ mutant displays altered sensitivities to various inhibitors of sphingolipid metabolism, i.e. myriocin and aureobasidin A. Sphingolipid profiling indicated that sch9 cells have increased levels of long-chain bases and long-chain base-1 phosphates, decreased levels of several species of (phyto)ceramides, and altered ratios of complex sphingolipids. We show that the TORC1 – Sch9 signalling pathway functions to repress the expression of the ceramidase genes YDC1 and YPC1, thereby unveiling, for the first time in yeast, a nutrient-dependent transcriptional mechanism involved in the regulation of sphingolipid metabolism. Additionally, we established that Sch9 affects the activity of the inositol phosphosphingolipid phospholipase C, Isc1, which is required for ceramide production by hydrolysis of complex sphingolipids. As sphingolipid metabolites play a crucial role in the regulation of stress tolerance and longevity of yeast cells, our data provide a model in which Sch9 regulates the latter phenotypes by acting not only as an effector but also as a regulator of sphingolipid metabolism.