Metabolism and Regulation of Glycerolipids in Yeast

Abstract

Bilayer-forming phospholipids and storage lipids like triacylglycerol are all part of the lipid class known as glycerolipids. Research conducted in the model organism Saccharomyces cerevisiae has been at the forefront of the identification of the enzymes involved in the metabolism of glycerolipids and its regulation. The initial two sequential acylations of glycerol 3-phosphate using acyl-CoA as acyl donor to produce phosphatidic acid (PA) are common steps in the de novo synthesis of glycerolipids. PA represents a critical branching point in this pathway as it can either be (1) dephosphorylated to produce diacylglycerol (DAG) for the synthesis of triacylglycerol or phospholipids through the Kennedy pathways or (2) be converted to CDP-DAG for the synthesis of phospholipids. PA has surfaced as not only the precursor for all glycerolipids but also as a potent signalling lipid able to integrate cellular cues to balance synthesis of phospholipids for membrane expansion versus storage in the form of triacylglycerol. The PA-dependent regulatory circuit Ino2-Ino4-Opi1 that controls expression of enzymes involved in glycerolipid synthesis downstream of the PA branching point has been very well characterized in yeast. Less is known about the regulation of the upstream initial steps leading to PA synthesis. Emerging research points to the production of different pools of PA by the acyltransferases in charge of the initial acylation steps in concert with other pathways that produce and use acyl-CoAs. In addition, recent discoveries on the movement of PA between organelles further indicate these pools are mobile. Although elucidation of lipid pool partitioning remains a major challenge in the field, current technology combined with the tractability of yeast warrant future progress on this topic.