Coordination of Storage Lipid Synthesis and Membrane Biogenesis EVIDENCE FOR CROSS-TALK BETWEEN TRIACYLGLYCEROL METABOLISM AND PHOSPHATIDYLINOSITOL SYNTHESIS

Despite the importance of triacylglycerols (TAG) and steryl esters (SE) in phospholipid synthesis in cells transitioning from stationary-phase into active growth, there is no direct evidence for their requirement in synthesis of phosphatidylinositol (PI) or other membrane phospholipids in logarithmically growing yeast cells. We report that the dga1 Delta lro1 Delta are1 Delta are2 Delta strain, which lacks the ability to synthesize both TAG and SE, is not able to sustain normal growth in the absence of inositol (Ino(-) phenotype) at 37 degrees C especially when choline is present. Un-like many other strains exhibiting an Ino(-) phenotype, the dga1 Delta lro1 Delta are1 Delta are2 Delta strain does not display a defect in INO1 expression. However, the mutant exhibits slow recovery of PI content compared with wild type cells upon reintroduction of inositol into logarithmically growing cultures. The tgl3 Delta tgl4 Delta tgl5 Delta strain, which is able to synthesize TAG but unable to mobilize it, also exhibits attenuated PI formation under these conditions. However, unlike dga1 Delta lro1 Delta are1 Delta are2 Delta, the tgl3 Delta tgl4 Delta tgl5 Delta strain does not display an Ino(-) phenotype, indicating that failure to mobilize TAG is not fully responsible for the growth defect of the dga1 Delta lro1 Delta are1 Delta are2 Delta strain in the absence of inositol. Moreover, synthesis of phospholipids, especially PI, is dramatically reduced in the dga1 Delta lro1 Delta are1 Delta are2 Delta strain even when it is grown continuously in the presence of inositol. The mutant also utilizes a greater proportion of newly synthesized PI than wild type for the synthesis of inositol-containing sphingolipids, especially in the absence of inositol. Thus, we conclude that storage lipid synthesis actively influences membrane phospholipid metabolism in logarithmically growing cells.