Requirement of a specific group of sphingolipid‐metabolizing enzyme for growth of yeast Saccharomyces cerevisiae under impaired metabolism of glycerophospholipids

Summary Sphingolipids play critical roles in many physiologically important events in yeast Saccharomyces cerevisiae . In this study, we screened for yeast mutants showing high sensitivity to Aureobasidin A, an inhibitor of inositol phosphorylceramide synthase, and found that a lack of SAC1 encoding phosphoinositides phosphatase causes high sensitivity to the inhibitor. Double mutation analysis involving the SAC1 and non‐essential sphingolipid‐metabolizing enzyme genes revealed that csg1 Δ, csg2 Δ, ipt1 Δ or scs7 Δ causes synthetic lethality with deletion of SAC1 . As previously reported, SAC1‐ repressed cells exhibited a reduced cellular phosphatidylserine (PS) level, and overexpression of PSS1 encoding PS synthase complemented the growth defects of scs7 Δ, csg1 Δ and ipt1 Δ cells under SAC1‐ repressive conditions. Furthermore, repression of PSS1 expression resulted in synthetic growth defect with the deletion of CSG1 , IPT1 or SCS7 . The growth defects of scs7 Δ, csg1 Δ and ipt1 Δ cells under SAC1‐ or PSS1‐ repressive conditions were also complemented by overexpression of Arf‐GAP AGE1 , which encodes a protein related to membrane trafficking. Under SAC1‐ repressive conditions, scs7 Δ, csg1 Δ and ipt1 Δ cells showed defects in vacuolar morphology, which were complemented by overexpression of each of PSS1 and AGE1. These results suggested that a specific group of sphingolipid‐metabolizing enzyme is required for yeast cell growth under impaired metabolism of glycerophospholipids.