Regulation of Yeast Pah1 Phosphatidate Phosphatase in Lipid Synthesis

Abstract

In the yeast Saccharomyces cerevisiae, the synthesis of phospholipids in the exponential phase of growth occurs at the expense of the storage lipid triacylglycerol. As cells progress into the stationary phase, the synthesis of triacylglycerol occurs at the expense of phospholipids. Pah1 phosphatidate phosphatase plays an important role in this metabolism; the enzyme produces the diacylglycerol needed for the synthesis of triacylglycerol and simultaneously controls the level of phosphatidate for the synthesis of phospholipids. Loss of Pah1 results in severe phenotypes that include aberrant nuclear/endoplasmic reticulum membrane expansion, cell wall fragility, reduction in lipid droplets, vacuole fragmentation, fatty acid‐induced lipotoxicity, susceptibility to oxidative stress, and loss of chronological life span. PAH1 expression is induced throughout growth and the induction in the stationary phase is stimulated by inositol supplementation. Pah1 phosphatidate phosphatase activity is modulated by phospholipids, sphingoid bases, nucleotides, and through the phosphorylation and dephosphorylation of the enzyme, as well as by proteasome‐mediated degradation. The proteasomal degradation of Pah1, which occurs by ubiquitin‐dependent and ‐independent mechanisms, is governed by the phosphorylation/dephosphorylation of the enzyme.Support or Funding InformationSupported by National Institutes of Health grants R37‐GM028140‐33 and R01‐GM050679‐22.