Sch9, the orthologue of mammalian PKB, acts as a regulator of the sphingolipid rheostat in Saccharomyces cerevisiae

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. In line with this, cells lacking Sch9 showed 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. Genetic and biochemical analysis confirmed that Sch9 plays a critical role in ceramide homeostasis by controlling de novo ceramide synthesis, through regulating ceramidase levels downstream of TORC1, as well as regulating the activity of the inositol phosphosphingolipid phospholipase C, Isc1, which is required for ceramide production by hydrolysis of complex sphingolipids. The balance between de novo and hydrolytic ceramide synthesis is crucial for survival and dictates the stress tolerance and longevity of yeast cells. Together our data indicate that Sch9 is not only an effector but also a regulator of sphingolipid metabolism.status: publishe