Regulation of phospholipid synthesis in yeast

Abstract

Phospholipid synthesis in the yeast Saccharomyces cerevisiae is a complex process that involves regulation by both genetic and biochemical mechanisms. The activity levels of phospholipid synthesis enzymes are controlled by gene expression (e.g., transcription) and by factors (lipids, water-soluble phospholipid precursors and products, and covalent modification of phosphorylation) that modulate catalysis. Phosphatidic acid, whose levels are controlled by the biochemical regulation of key phospholipid synthesis enzymes, plays a central role in the regulation of phospholipid synthesis gene expression.

Fig. 1.

Phospholipid synthesis pathways in S. cerevisiae. The pathways shown for the synthesis of phospholipids include the relevant steps discussed in this review. The synthesis of PE and PC from lysoPE and lysoPC, respectively, is not shown in the figure. The genes that are known to encode enzymes catalyzing individual steps in the lipid synthesis pathways are indicated. The UAS_INO-containing genes that are subject to regulation by the Ino2-Ino4 activation complex and the Opi1 repressor are blue. Gro, glycerol; DHAP, dihydroxyacetone phosphate; Glu, glucose; Ins, inositol; PME, phosphatidylmonomethylethanolamine; PDE, phosphatidyldimethylethanolamine; Etn, ethanolamine; Cho, choline.

Fig. 2.

Model for the biochemical regulation of phospholipid synthesis. The upper portion of the diagram shows the major steps in the synthesis of phospholipids. The key enzymes (PMT, CHO2-encoded PE methyltransferase and OPI3-encoded phospholipid methyltransferase; PIS, PIS1-encoded PI synthase; PSS, CHO1-encoded PS synthase; PAP, PAH1-encoded PA phosphatase; DGK, DGK1-encoded DAG kinase) that are biochemically regulated by phospholipid precursors and products are highlighted by the blue ellipses. The bottom portion of the diagram shows the transcriptional activation of UAS_INO-containing genes (blue) by the Ino2-Ino4 complex. Elevated PA (highlighted in yellow) content prevents the translocation of Opi1 into the nucleus, and thus its repressor function of UAS_INO-containing phospholipid synthesis genes. The color green designates stimulation, whereas the color red designates inhibition.