Yeast Pah1 Phosphatidate Phosphatase Regulates the Expression of the CHO1 ‐encoded Phosphatidylserine Synthase for Membrane Phospholipid Synthesis

Pah1 phosphatidate (PA) phosphatase catalyzes the committed step for the synthesis of triacylglycerol, whereas Cho1 phosphatidylserine (PS) synthase catalyzes the committed step for the synthesis of membrane phospholipids. In the exponential phase, the expression of Cho1 PS synthase is largely governed by the cellular concentration of PA and the Ino2/Ino4/Opi1 regulatory circuit acting on the UAS INO cis ‐acting element in the CHO1 promoter. In this work, we examined the effect of the PA‐controlling Pah1 PA phosphatase on the expression of Cho1 PS synthase. Compared with the wild type control, the pah1 Δ mutant in the exponential phase exhibited elevated levels of Cho1 PS synthase. In the stationary phase when Cho1 PS synthase expression was repressed in wild type, the enzyme expression in the pah1 Δ mutant was further induced over that observed in the exponential phase. Analysis of the CHO1 promoter by its deletion and site‐directed mutation indicated that the expression of Cho1 PS synthase in the pah1 Δ mutant was elevated by transcriptional regulation through the UAS INO element. Lipid analysis showed that the increased phospholipid synthesis in the pah1 Δ mutant was significantly reduced by the expression of a UAS INO ‐deficient CHO1 allele. These results indicate that Pah1 PA phosphatase activity plays a major role in the regulation of Cho1 PS synthase expression through the UAS INO ‐mediated transcriptional control. Supported by NIH grant GM028140.