Regulation of CDP-diacylglycerol synthesis and utilization by inositol and choline in Schizosaccharomyces pombe

Abstract

CDP-diacylglycerol (CDP-DG (12,20). In particular, relative amounts of the major anionic phospholipids phosphatidylinositol (PI) and phosphatidylserine (PS) vary in response to the exogenous inositol concentration (12). Thus, when the inositol concentration is low, PI content is decreased while PS content is increased. The precursor to the synthesis of PI and PS is CDP-diacylglycerol (CDP-DG) (Fig. 1). This liponucleotide is an important intermediate in yeast phospholipid synthesis, as it is the direct source of the phosphatidyl moiety in phosphatidylglycerolphosphate (PGP), PI, and PS. PGP is then converted to phosphatidylglycerol and cardiolipin, while PS is converted to phosphatidylethanolamine (PE) and phosphatidylcholine (PC) (7). As CDP-DG is located at a crucial branchpoint in phospholipid synthesis, differential regulation of the enzymes which metabolize it may account for the changes in phospholipid composition observed in response to different physiological conditions.In Saccharomyces cerevisiae, the enzymes which synthesize and utilize CDP-DG are regulated on many levels. Inositol is a key regulator of phospholipid biosynthesis in this lower eucaryote (reviewed in references 7 arid 33). The pathway for conversion of phosphatidate, phosphatidate -)

Cardiolipin synthase expression is essential for growth at elevated temperature and is regulated by factors affecting mitochondrial development

“…As this is the rate‐limiting step in CL synthesis, there is no need to regulate Cls1p synthesis in the same manner. Consistent with this hypothesis is the observation that, in Schizosaccharomyces pombe, the activity of PI synthase increases, while Pgs1p decreases upon the addition of inositol to growth media (Gaynor and Greenberg, 1992). An increase in PI synthase activity leads to an increase in PI, which inhibits the activity of the partially purified Pgs1p (Jiang et al ., 1998).…”

Gene Expression of Pneumocystis murina after Treatment with Anidulafungin Results in Strong Signals for Sexual Reproduction, Cell Wall Integrity, and Cell Cycle Arrest, Indicating a Requirement for Ascus Formation for Proliferation

“…Interestingly, starvation for inositol resulted in a 3-fold increase in CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase expression in S. pombe ( 33 ). Like S. pombe , Pneumocystis species are myo -inositol auxotrophs, and the upregulation of the gene coding for this protein may indicate an increased need for this essential nutrient in this stressed environment.…”

Increase in cellular triacylglycerol content and emergence of large ER-associated lipid droplets in the absence of CDP-DG synthase function

“…Possible reasons for this apparent inconsistency include differences in experimental setup (e.g., transcriptional shut-off of Cds1 in budding yeast versus conditional loss-of-function mutant in fission yeast) and divergent lipid signaling and metabolism in budding and fission yeasts ( Raychaudhuri et al ., 2012 ). As an example, the PA-responsive gene regulation circuitry controlling inositol production and phospholipid biosynthesis is not conserved between budding and fission yeast; in fact, the fission yeasts are naturally auxotrophic for inositol ( Fernandez et al ., 1986 ; Gaynor and Greenberg, 1992 ; Ingavale and Bachhawat, 1999 ).…”