Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biotechnology & Applied Microbiology, Microbiology, Mycology, 0605 Microbiology, 0699 Other Biological Sciences, 1003 Industrial Biotechnology, 3107 Microbiology

Abstract:

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 further elaborated in vivo. Sphingolipid profiling indicated that cells lacking Sch9 have increased levels of long chain bases and long chain base 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 a regulator of sphingolipid metabolism.