Differential roles of Opi1 and Pah1 in the metabolism and regulation of phospholipid biosynthetic genes

Abstract

In yeast, phosphatidic acid (PA), a common metabolic precursor to both phospholipids and triacylglycerol, influences the localization of Opi1, a negative regulator of transcription of phospholipid biosynthetic genes. PA levels are also regulated in part by the activity of the yeast lipin Pah1. We are investigating the extent to which Opi1 and Pah1 compete for the same PA pool in the endoplasmic reticulum. Since changes in PA levels regulate expression of phospholipid biosynthetic genes, such as INO1, we analyzed the derepression of this gene in wild type and pah1Δ strains during the transition from inositol supplementation to medium lacking inositol. Wild type cells exhibit a peak of INO1 derepression at about 3 hours after removal of inositol while the pah1Δ strain reaches its maximum at 5 hours. In both strains INO1 expression decreased precipitously after reaching its peak. We are currently exploring the relationships between changes in PA content and relocalization of Opi1 to the perinuclear endoplasmic reticulum in wild type, pah1Δ and a series of Pah1 nonphosphorylatable alanine mutants from Carman laboratory.Supported by NIH grant GM‐19629 to SAH