The glycerophosphocholine acyltransferase Gpc1 is part of a phosphatidylcholine (PC)-remodeling pathway that alters PC species in yeast

Abstract

Edited by George M. CarmanPhospholipase B-mediated hydrolysis of phosphatidylcholine (PC) results in the formation of free fatty acids and glycerophosphocholine (GPC) in the yeast Saccharomyces cerevisiae. GPC can be reacylated by the glycerophosphocholine acyltransferase Gpc1, which produces lysophosphatidylcholine (LPC), and LPC can be converted to PC by the lysophospholipid acyltransferase Ale1. Here, we further characterized the regulation and function of this distinct PC deacylation/reacylation pathway in yeast. Through in vitro and in vivo experiments, we show that Gpc1 and Ale1 are the major cellular GPC and LPC acyltransferases, respectively. Importantly, we report that Gpc1 activity affects the PC species profile. Loss of Gpc1 decreased the levels of monounsaturated PC species and increased those of diunsaturated PC species, whereas Gpc1 overexpression had the opposite effects. Of note, Gpc1 loss did not significantly affect phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine profiles. Our results indicate that Gpc1 is involved in postsynthetic PC remodeling that produces more saturated PC species. qRT-PCR analyses revealed that GPC1 mRNA abundance is regulated coordinately with PC biosynthetic pathways. Inositol availability, which regulates several phospholipid biosynthetic genes, down-regulated GPC1 expression at the mRNA and protein levels and, as expected, decreased levels of monounsaturated PC species. Finally, loss of GPC1 decreased stationary phase viability in inositol-free medium. These results indicate that Gpc1 is part of a postsynthetic PC deacylation/reacylation remodeling pathway (PC-DRP) that alters the PC species profile, is regulated in coordination with other major lipid biosynthetic pathways, and affects yeast growth.

Antibacterial Activity and Mechanism of Linalool against Shewanella putrefaciens

“…This product is an intermediate of phospholipid metabolism and a precursor of phosphatidylcholine and acetylcholine synthesis. GPC can be re-acylated by glycerophosphocholine acyltransferase Gpc1 to produce lysophosphatidylcholine (LPC), which can be transformed into phosphatidylcholine (PC) by lysophospholipid acyltransferase Ale1 [ 46 ]. PC and phosphatidyl ethanolamine (PE) are the main phospholipids in the plasma membrane and are important for membrane integrity and fluidity; PE can enhance membrane thickness to improve the resistance of cells to environmental stress [ 47 , 48 ].…”

Mechanisms and functions of membrane lipid remodeling in plants

“…The yeast gene encoding GPCAT was identified by screening enzyme activities of extracts from a yeast knockout library (Glab et al ., 2016). Loss of GPCAT affects PC fatty acid profiles, suggesting a role of this enzyme in post‐synthetic acyl remodeling of PC (Anaokar et al ., 2019). The plant GPCAT has been shown to exhibit broad substrate specificity for acyl donors (Glab et al ., 2016).…”

Serum Metabolic Profiling of Late-Pregnant Women With Antenatal Depressive Symptoms

“…PC is the most abundant phospholipid of all mammalian cell types and subcellular organelles, accounting for 40–50% of total cellular phospholipids ( 22 , 37 ). LysoPC, an intermediate of PC metabolism, is produced by the cleavage of PC by phospholipase A2 (PLA2) ( 42 ), and LysoPC is converted back to PC via lysophosphatidylcholine acyltransferase ( 43 ). Then, LysoPC is orderly deacylated to glycerol–phosphocholine and choline by lysophospholipase I and glycerol–phosphocholine phosphodiesterase via glycerophospholipid metabolism pathway ( 44 ).…”