Lipid Acyl Chain Remodeling in Yeast

Abstract

Membrane lipid homeostasis is maintained by de novo synthesis, intracellular transport, remodeling, and degradation of lipid molecules. Glycerophospholipids, the most abundant structural component of eukaryotic membranes, are subject to acyl chain remodeling, which is defined as the post-synthetic process in which one or both acyl chains are exchanged. Here, we review studies addressing acyl chain remodeling of membrane glycerophospholipids in Saccharomyces cerevisiae, a model organism that has been successfully used to investigate lipid synthesis and its regulation. Experimental evidence for the occurrence of phospholipid acyl chain exchange in cardiolipin, phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine is summarized, including methods and tools that have been used for detecting remodeling. Progress in the identification of the enzymes involved is reported, and putative functions of acyl chain remodeling in yeast are discussed.

Keywords: acyl chain exchange; acyltransferases; lipid homeostasis; membrane lipids; phospholipases; transacylases.

Figure 1

Biosynthesis and acyl chain remodeling of CL in yeast mitochondria with the enzymes indicated in blue. Abbreviations: PA, phosphatidic acid; CDP-DG, CDP-diacylglycerol; PGP, phosphatidylglycerolphosphate; PG, phosphatidylglycerol; MLCL, monolysocardiolipin; PL, phospholipid.

Figure 2

Metabolism of PC in yeast with the enzymes indicated in blue. Acyl chain remodeling of PC may proceed by deacylation to lyso-PC and/or GPC catalyzed by the PLBs Plb1p and Nte1p and/or by PLA and/or PLB that remain to be assigned. Subsequently, lyso-PC can be reacylated by the 1-acyl lyso-PC acyltransferase Ale1p. Acyl-CoA-dependent acyltransferases attaching an acyl chain at the sn-1 position remain to be identified. Alternatively, the de- and reacylation reactions could be catalyzed by transacylases (not shown). The biosynthesis routes of PC are indicated by the dashed arrows.

Figure 3

Time course of PC remodeling in live yeast cells at 30°C as recorded by ESI-MS/MS in pulse-chase experiments addressing PC synthesized by methylation of PE. Cells from pct1 pYES2 (empty vector control) (A), pct1 pYES2-SCT1 (B), and pct1plb1 pYES2-SCT1 (C) strains cultured in galactose-containing medium to induce overexpression of SCT1 from the GAL1 promoter (B and C), were pulsed for 10 minutes with (methyl-D₃)-methionine. After rapid removal of the label, cells were chased in the presence of unlabeled methionine for the time intervals indicated. Molecular species profiles of (methyl-D₃)₃-PC and steady-state PC (blue bars) were analyzed by parent ion scanning of total lipid extracts in the positive ion mode at m/z 193 and 184, respectively (molecular species of PC are indicated by the total number of acyl carbon atoms:total number of double bonds). The overexpression of Sct1p slows down growth. The experimental conditions were such that the doubling time of the overexpressing strains was approximately 1.3× that of the empty vector control; deletion of PLB1 did not affect the growth rate. Data were taken from ref. .