Metabolism and Regulation of Glycerolipids in the Yeast Saccharomyces cerevisiae

Abstract

Due to its genetic tractability and increasing wealth of accessible data, the yeast Saccharomyces cerevisiae is a model system of choice for the study of the genetics, biochemistry, and cell biology of eukaryotic lipid metabolism. Glycerolipids (e.g., phospholipids and triacylglycerol) and their precursors are synthesized and metabolized by enzymes associated with the cytosol and membranous organelles, including endoplasmic reticulum, mitochondria, and lipid droplets. Genetic and biochemical analyses have revealed that glycerolipids play important roles in cell signaling, membrane trafficking, and anchoring of membrane proteins in addition to membrane structure. The expression of glycerolipid enzymes is controlled by a variety of conditions including growth stage and nutrient availability. Much of this regulation occurs at the transcriptional level and involves the Ino2–Ino4 activation complex and the Opi1 repressor, which interacts with Ino2 to attenuate transcriptional activation of UASINO-containing glycerolipid biosynthetic genes. Cellular levels of phosphatidic acid, precursor to all membrane phospholipids and the storage lipid triacylglycerol, regulates transcription of UASINO-containing genes by tethering Opi1 to the nuclear/endoplasmic reticulum membrane and controlling its translocation into the nucleus, a mechanism largely controlled by inositol availability. The transcriptional activator Zap1 controls the expression of some phospholipid synthesis genes in response to zinc availability. Regulatory mechanisms also include control of catalytic activity of glycerolipid enzymes by water-soluble precursors, products and lipids, and covalent modification of phosphorylation, while in vivo function of some enzymes is governed by their subcellular location. Genome-wide genetic analysis indicates coordinate regulation between glycerolipid metabolism and a broad spectrum of metabolic pathways.

Arabidopsis Lipins, PDAT1 Acyltransferase, and SDP1 Triacylglycerol Lipase Synergistically Direct Fatty Acids toward β-Oxidation, Thereby Maintaining Membrane Lipid Homeostasis

“…Because phospholipid levels are elevated in both tgd1-1 sdp1-4, in which TAG hydrolysis is impaired, and tgd1-1 pxa1-2, in which FA degradation is impaired, it is unlikely that this increase is due to the augmented recycling to TAG into membrane lipids as a result of blocked FA turnover. It is important to note that lipid homeostatic regulation in bacteria (Zhang and Rock, 2008), yeast (Henry et al, 2012), and mammals (Hermansson et al, 2011) is complex and occurs by diverse mechanisms. While we have shown that PDAT1, SDP1 lipase, and lipins are involved in this process in leaves, it is likely that additional components will be uncovered in future research that will lead to a more global understanding of lipid homeostasis in plants.…”

“…To date, although most of the enzymatic steps in lipid biosynthesis are defined at the moleculargenetic level in several model organisms (Nohturfft and Zhang, 2009;Chapman and Ohlrogge, 2012;Henry et al, 2012), the signals and mechanisms regulating intracellular lipid homeostasis are less well defined (Nohturfft and Zhang, 2009;Hermansson et al, 2011, Holthuis andMenon, 2014), particularly in plants (Bonaventure et al, 2004;Kunz et al, 2009;Zhang et al, 2009;Fan et al, 2013a;Park et al, 2013).…”

ER-shaping proteins facilitate lipid exchange between the ER and mitochondria in S. cerevisiae

“…The most likely explanation for this is that some of the radiolabel from [ 3 H]serine can be incorporated into PE by mechanisms other than decarboxylation of PS. Serine is used in the biosynthesis of sphingosine and degradation of the sphingosine derivative dihydrosphingosine-1-phosphate by Dpl1p yields ethanolamine phosphate (Henry et al, 2012 (Raychaudhuri and Prinz, 2008). Thus, the percentage of [ 3 H]PS converted to PE in psd1D psd2D cells is the lowest that can be achieved when PS decarboxylation is ablated.…”

“…Thus, the increased amount of PS transfer from ER to mitochondria in cells expressing ChiMERA resulted in an increased steady-state level of PE. Since CDP-diacylglycerol is a precursor for both PI and PS (Henry et al, 2012), it may be that increased PE production from PS in cells expressing ChiMERA depletes the pools of CDP-diacylglycerol available for PI biosynthesis. It was not possible to determine phospholipids levels were altered in the mitochondria from cells expressing ChiMERA since we were unable to isolate purified mitochondria from these cells (not shown), perhaps because they have a substantially increased amount of ER-derived membranes associated with them.…”

Morphogenesis checkpoint kinase Swe1 is the executor of lipolysis-dependent cell-cycle progression

“…Degradation of TG in yeast is governed by the major lipid droplet (LD)-associated lipases, encoded by TGL3 and TGL4 (4, 12); both enzymes belong to the patatin-domaincontaining family of proteins, members of which play a crucial role in lipid homeostasis also in mammals (13). Multiple additional lipases exist in yeast, but their specific function and contribution to TG homeostasis may be restricted to specific growth conditions (7,14,15).Absence of lipolysis in mutants lacking TGL3 and TGL4 results in up to threefold elevated levels of TG and reduced levels of phosphatidylcholine and sphingolipids (4,12,16,17), indicating that TG breakdown provides precursors for these lipids or generates some regulatory factors required for their synthesis. The rate of phosphatidylinositol (PI) synthesis after readdition of inositol to inositol-starved cells is reduced by 50% in lipase-deficient cells; the boost of PI synthesis under inositol refeeding conditions is completely abolished if de novo FA synthesis is additionally blocked in the lipase mutants by the inhibitor cerulenin (18).…”