Abstract
Triacylglycerol (TAG) is the major storage component for fatty acids, and thus for energy, in eukaryotic cells. In this mini-review, we describe recent progress that has been made with the yeast Saccharomyces cerevisiae in understanding formation of TAG and its cell biological role. Formation of TAG involves the synthesis of phosphatidic acid (PA) and diacylglycerol (DAG), two key intermediates of lipid metabolism. De novo formation of PA in yeast as in other types of cells can occur either through the glycerol-3-phosphate- or dihydroxyacetone phosphate-pathways—each named after its respective precursor. PA, formed in two steps of acylation, is converted to DAG by phosphatidate phosphatase. Acylation of DAG to yield TAG is catalyzed mainly by the two yeast proteins Dga1p and Lro1p, which utilize acyl-CoA or phosphatidylcholine, respectively, as acyl donors. In addition, minor alternative routes of DAG acylation appear to exist. Endoplasmic reticulum and lipid particles (LP), the TAG storage compartment in yeast, are the major sites of TAG synthesis. The interplay of these organelles, formation of LP, and enzymatic properties of enzymes catalyzing the synthesis of PA, DAG, and TAG in yeast are discussed in this communication.
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References
Achleitner G, Gaigg B, Krasser A, Kainersdorfer E, Kohlwein SD, Perktold A, Zellnig G, Daum G (1999) Association between the endoplasmic reticulum and mitochondria of yeast facilitates interorganelle transport of phospholipids through membrane contact. Eur J Biochem 264:545–553
Athenstaedt K, Daum G (1997) Biosynthesis of phosphatidic acid in lipid particles and endoplasmic reticulum of Saccharomyces cerevisiae. J Bacteriol 179:7611–7616
Athenstaedt K, Daum G (2000) 1-Acyldihydroxyacetone-phosphate reductase (Ayr1p) of the yeast Saccharomyces cerevisiae encoded by the open reading frame YIL124w is a major component of lipid particles. J Biol Chem 275:235–240
Athenstaedt K, Weys S, Paltauf F, Daum G (1999a) Redundant systems of phosphatidic acid biosynthesis via acylation of glycerol-3-phosphate or dihydroxyacetone phosphate in the yeast Saccharomyces cerevisiae. J Bacteriol 181:1458–1463
Athenstaedt K, Zweytick D, Jandrositz A, Kohlwein SD, Daum G (1999b) Identification and characterization of major lipid particle proteins of the yeast Saccharomyces cerevisiae. J Bacteriol 181:6441–6448
Carman GM (1997) Phosphatidate phosphatases and diacylglycerol pyrophosphate phosphatases in Saccharomyces cerevisiae and Escherichia coli. Biochim Biophys Acta 1348:45–55
Carman GM, Henry SA (1999) Phospholipid biosynthesis in the yeast Saccharomyces cerevisiae and interrelationship with other metabolic processes. Prog Lipid Res 38:361–399
Carman GM, Zeimetz GM (1996) Regulation of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae. J Biol Chem 271:13293–13296
Cases S, Smith SJ, Zheng YW, Myers HM, Lear SR, Sande E, Novak S, Collins C, Welch CB, Lusis AJ, Erickson SK, Farese RV Jr (1998) Identification of a gene encoding an acyl-CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis. Proc Natl Acad Sci USA 95:13018–13023
Cases S, Stone SJ, Zhou P, Yen E, Tow B, Lardizabal KD, Voelker T, Farese RV Jr (2001) Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members. J Biol Chem 276:38870–38876
Christiansen K (1978) Triacylglycerol synthesis in lipid particles from baker's yeast (Saccharomyces cerevisiae). Biochim Biophys Acta 530:78–90
Christiansen K (1979) Utilization of endogenous diacylglycerol for the synthesis of triacylglycerol, phosphatidylcholine and phosphatidylethanolamine by lipid particles from baker's yeast (Saccharomyces cerevisiae). Biochim Biophys Acta 574:448–460
Dahlqvist A, Stahl U, Lenman M, Banas A, Lee M, Sandager L, Ronne H, Stymne S (2000) Phospholipid:diacylglycerol acyltransferase: an enzyme that catalyzes the acyl-CoA-independent formation of triacylglycerol in yeast and plants. Proc Natl Acad Sci USA 97:6487–6492
Daum G, Paltauf F (1980) Triacylglycerols as fatty acid donors for membrane phopholipid biosynthesis in yeast. Monatsh Chem 111:355–363
Daum G, Lees ND, Bard M, Dickson R (1998) Biochemistry, cell biology and molecular biology of lipids of Saccharomyces cerevisiae. Yeast 14:1471–1510
Daum G, Tuller G, Nemec T, Hrastnik C, Balliano G, Cattel L, Milla P, Rocco F, Conzelmann A, Vionnet C, Kelly DE, Kelly S, Schweizer E, Schuller HJ, Hojad U, Greiner E, Finger K (1999) Systematic analysis of yeast strains with possible defects in lipid metabolism. Yeast 15:601–614
Dodds PF (1995) Xenobiotic lipids: the inclusion of xenobiotic compounds in pathways of lipid biosynthesis. Prog Lipid Res 34:219–247
Faulkner A, Chen X, Rush J, Horazdovsky B, Waechter CJ, Carman GM, Sternweis PC (1999) The LPP1 and DPP1 gene products account for most of the isoprenoid phosphate phosphatase activities in Saccharomyces cerevisiae. J Biol Chem 274:14831–14837
Furneisen JM, Carman GM (2000) Enzymological properties of the LPP1-encoded lipid phosphatase from Saccharomyces cerevisiae. Biochim Biophys Acta 1484:71–82
Gaigg B, Simbeni R, Hrastnik C, Paltauf F, Daum G (1995) Characterization of a microsomal subfraction associated with mitochondria of the yeast, Saccharomyces cerevisiae. Involvement in synthesis and import of phospholipids into mitochondria. Biochim Biophys Acta 1234:214–220
Gangar A, Karande AA, Rajasekharan R (2001a) Isolation and localization of a cytosolic 10 S triacylglycerol biosynthetic multienzyme complex from oleaginous yeast. J Biol Chem 276:10290–10298
Gangar A, Karande AA, Rajasekharan R (2001b) Purification and characterization of acyl-acyl carrier protein synthetase from oleaginous yeast and its role in triacylglycerol biosynthesis. Biochem J 360:471–479
Gangar A, Raychaudhuri S, Rajasekharan R (2002) Alteration in the cytosolic triacylglycerol biosynthetic machinery leads to decreased cell growth and triacylglycerol synthesis in oleaginous yeast. Biochem J 365:577–589
Gasch AP, Spellman PT, Kao CM, Carmel-Harel O, Eisen MB, Storz G, Botstein D, Brown PO (2000) Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 11:4241–4257
Gotto AM Jr (1998) Triglyceride as a risk factor for coronary artery disease. Am J Cardiol 82:22Q–25Q
Han GS, Johnston CN, Chen X, Athenstaedt K, Daum G, Carman GM (2001) Regulation of the Saccharomyces cerevisiae DPP1-encoded diacylglycerol pyrophosphate phosphatase by zinc. J Biol Chem 276:10126–10133
Han G, Gable K, Kohlwein SD, Beaudoin F, Napier JA, Dunn TM (2002) The Saccharomyces cerevisiae YBR159w gene encodes the 3-ketoreductase of the microsomal fatty acid elongase. J Biol Chem 277:35440–35449
Hobbs DH, Lu C, Hills MJ (1999) Cloning of a cDNA encoding diacylglycerol acyltransferase from Arabidopsis thaliana and its functional expression. FEBS Lett 452:145–149
Hosaka K, Yamashita S (1984a) Partial purification and properties of phosphatidate phosphatase in Saccharomyces cerevisiae. Biochim Biophys Acta 796:102–109
Hosaka K, Yamashita S (1984b) Regulatory role of phosphatidate phosphatase in triacylglycerol synthesis of Saccharomyces cerevisiae. Biochim Biophys Acta 796:110–117
Huijbregts RP, Topalof L, Bankaitis VA (2000) Lipid metabolism and regulation of membrane trafficking. Traffic 1:195–202
Katagiri T, Shinozaki K (1998) Disruption of a gene encoding phosphatidic acid phosphatase causes abnormal phenotypes in cell growth and abnormal cytokinesis in Saccharomyces cerevisiae. Biochem Biophys Res Commun 248:87–92
Kelley MJ, Carman GM (1987) Purification and characterization of CDP–diacylglycerol synthase from Saccharomyces cerevisiae. J Biol Chem 262:14563–14570
Kent C (1995) Eukaryotic phospholipid biosynthesis. Annu Rev Biochem 64:315–343
Kocsis MG, Weselake RJ (1996) Phosphatidate phosphatases of mammals, yeast, and higher plants. Lipids 31:785–802
Krauss RM (1998) Triglycerides and atherogenic lipoproteins: rationale for lipid management. Am J Med 105:58S–62S
Kuchler K, Daum G, Paltauf F (1986) Subcellular and submitochondrial localization of phospholipid-synthesizing enzymes in Saccharomyces cerevisiae. J Bacteriol 165:901–910
Lacey DJ, Beaudoin F, Dempsey CE, Shewry PR, Napier JA (1999) The accumulation of triacylglycerols within the endoplasmic reticulum of developing seeds of Helianthus annus. Plant J 17:397–405
Lardizabal KD, Mai JT, Wagner NW, Wyrick A, Voelker T, Hawkins DJ (2001) DGAT2 is a new diacylglycerol acyltransferase gene family: purification, cloning, and expression in insect cells of two polypeptides from Mortierella ramanniana with diacylglycerol acyltransferase activity. J Biol Chem 276:38862–38869
Leber R, Zinser E, Zellnig G, Paltauf F, Daum G (1994) Characterization of lipid particles of the yeast, Saccharomyces cerevisiae. Yeast 10:1421–1428
Lehner R, Kuksis A (1996) Biosynthesis of triacylglycerols. Prog Lipid Res 35:169–201
Lin YP, Carman GM (1989) Purification and characterization of phosphatidate phosphatase from Saccharomyces cerevisiae. J Biol Chem 264:8641–8645
Liscovitch M, Czarny M, Fiucci G, Tang X (2000) Phospholipase D: molecular and cell biology of a novel gene family. Biochem J 345:401–415
Lyons TJ, Gasch AP, Gaither LA, Botstein D, Brown PO, Eide DJ (2000) Genome-wide characterization of the Zap1p zinc-responsive regulon in yeast. Proc Natl Acad Sci USA 97:7957–7962
Matsushita M, Nikawa J (1995) Isolation and characterization of a SCT1 gene which can suppress a choline-transport mutant of Saccharomyces cerevisiae. J Biochem (Tokyo) 117:447–451
Morlock KR, Lin YP, Carman GM (1988) Regulation of phosphatidate phosphatase activity by inositol in Saccharomyces cerevisiae. J Bacteriol 170:3561–3566
Munnik T, Musgrave A (2001) Phospholipid signaling in plants: holding on to phospholipase D. Sci STKE 111:PE42
Nagiec MM, Wells GB, Lester RL, Dickson RC (1993) A suppressor gene that enables Saccharomyces cerevisiae to grow without making sphingolipids encodes a protein that resembles an Escherichia coli fatty acyltransferase. J Biol Chem 268:22156–22163
Oelkers P, Tinkelenberg A, Erdeniz N, Cromley D, Billheimer JT, Sturley SL (2000) A lecithin cholesterol acyltransferase-like gene mediates diacylglycerol esterification in yeast. J Biol Chem 275:15609–15612
Oelkers P, Cromley D, Padamsee M, Billheimer JT, Sturley SL (2002) The DGA1 gene determines a second triglyceride synthetic pathway in yeast. J Biol Chem 277:8877–8881
Racenis PV, Lai JL, Das AK, Mullick PC, Hajra AK, Greenberg ML (1992) The acyl dihydroxyacetone phosphate pathway enzymes for glycerolipid biosynthesis are present in the yeast Saccharomyces cerevisiae. J Bacteriol 174:5702–5710
Rebecchi MJ, Pentyala SN (2000) Structure, function, and control of phosphoinositide-specific phospholipase C. Physiol Rev 80:1291–1335
Routaboul JM, Benning C, Bechtold N, Caboche M, Lepiniec L (1999) The TAG1 locus of Arabidopsis encodes for a diacylglycerol acyltransferase. Plant Physiol Biochem 37:831–840
Sandager L, Dahlqvist A, Banas A, Stahl U, Lenman M, Gustavsson M, Stymne S (2000) An acyl-CoA:cholesterol acyltransferase (ACAT)-related gene is involved in the accumulation of triacylglycerols in Saccharomyces cerevisiae. Biochem Soc Trans 28:700–702
Sandager L, Gustavsson MH, Stahl U, Dahlqvist A, Wiberg E, Banas A, Lenman M, Ronne H, Stymne S (2002) Storage lipid synthesis is non-essential in yeast. J Biol Chem 277:6478–6482
Smith SJ, Cases S, Jensen DR, Chen HC, Sande E, Tow B, Sanan DA, Raber J, Eckel RH, Farese RV Jr (2000) Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat Genet 25:87–90
Song S (2002) The role of increased liver triglyceride content: a culprit of diabetic hyperglycaemia? Diabetes Metab Res Rev 18:5–12
Sorger D, Daum G (2002) Synthesis of triacylglycerols by the acyl-coenzyme A:diacyl-glycerol acyltransferase Dga1p in lipid particles of the yeast Saccharomyces cerevisiae. J Bacteriol 184:519–524
Taskinen MR (1997) Triglyceride is the major atherogenic lipid in NIDDM. Diabetes Metab Rev 13:93–98
Taylor FR, Parks LW (1979) Triacylglycerol metabolism in Saccharomyces cerevisiae. Relation to phospholipid synthesis. Biochim Biophys Acta 575:204–214
Tillman TS, Bell RM (1986) Mutants of Saccharomyces cerevisiae defective in sn-glycerol-3-phosphate acyltransferase. Simultaneous loss of dihydroxyacetone phosphate acyltransferase indicates a common gene. J Biol Chem 261:9144–9149
Toke DA, Bennett WL, Oshiro J, Wu WI, Voelker DR, Carman GM (1998) Isolation and characterization of the Saccharomyces cerevisiae LPP1 gene encoding a Mg2+-independent phosphatidate phosphatase. J Biol Chem 273:14331–14338
Vance JE (1998) Eukaryotic lipid-biosynthetic enzymes: the same but not the same. Trends Biochem Sci 23:423–428
Van Heusden GP, Nebohacova M, Overbeeke TL, Steensma HY (1998) The Saccharomyces cerevisiae TGL2 gene encodes a protein with lipolytic activity and can complement an Escherichia coli diacylglycerol kinase disruptant. Yeast 14:225-232
Vico P, Cauet G, Rose K, Lathe R, Degryse E (2002) Dehydroepiandrosterone (DHEA) metabolism in Saccharomyces cerevisiae expressing mammalian steroid hydroxylase CYP7B: Ayr1p and Fox2p display 17beta-hydroxysteroid dehydrogenase activity. Yeast 19:873–886
Voelker DR (2000) Interorganelle transport of aminoglycerophospholipids. Biochim Biophys Acta 1486:97–107
Wagner S, Paltauf F (1994) Generation of glycerophospholipid molecular species in the yeast Saccharomyces cerevisiae. Fatty acid pattern of phospholipid classes and selective acyl turnover at sn-1 and sn-2 positions. Yeast 10:1429–1437
Wu WI, Carman GM (1996) Regulation of phosphatidate phosphatase activity from the yeast Saccharomyces cerevisiae by phospholipids. Biochemistry 35:3790–3796
Wu WI, Liu Y, Riedel B, Wissing JB, Fischl AS, Carman GM (1996) Purification and characterization of diacylglycerol pyrophosphate phosphatase from Saccharomyces cerevisiae. J Biol Chem 271:1868–1876
Yang H, Bard M, Bruner DA, Gleeson A, Deckelbaum RJ, Aljinovic G, Pohl TM, Rothstein R, Sturley SL (1996) Sterol esterification in yeast: a two-gene process. Science 272:1353–1356
Yang H, Cromley D, Wang H, Billheimer JT, Sturley SL (1997) Functional expression of a cDNA to human acyl-coenzyme A:cholesterol acyltransferase in yeast. Species-dependent substrate specificity and inhibitor sensitivity. J Biol Chem 272:3980–3985
Yu C, Kennedy NJ, Chang CC, Rothblatt JA (1996) Molecular cloning and characterization of two isoforms of Saccharomyces cerevisiae acyl-CoA:sterol acyltransferase. J Biol Chem 271:24157–24163
Yuan DS (2000) Zinc-regulated genes in Saccharomyces cerevisiae revealed by transposon tagging. Genetics 156:45–58
Zaremberg V, McMaster CR(2002) Differential partitioning of lipids metabolized by separate yeast glycerol-3-phosphate acyltransferases reveals that phospholipase D generation of phosphatidic acid mediates sensitivity to choline-containing lysolipids and drugs. J Biol Chem 277:39035–39044
Zheng Z, Zou J (2001) The initial step of the glycerolipid pathway: identification of glycerol 3-phosphate/dihydroxyacetone phosphate dual substrate acyltransferases in Saccharomyces cerevisiae. J Biol Chem 276:41710–41716
Zinser E, Sperka-Gottlieb CD, Fasch EV, Kohlwein SD, Paltauf F, Daum G (1991) Phospholipid synthesis and lipid composition of subcellular membranes in the unicellular eukaryote Saccharomyces cerevisiae. J Bacteriol 173:2026–2034
Zou J, Katavic V, Giblin EM, Barton DL, MacKenzie SL, Keller WA, Hu X, Taylor DC (1997) Modification of seed oil content and acyl composition in the Brassicaceae by expression of a yeast sn-2 acyltransferase gene. Plant Cell 9:909–923
Zou J, Wei Y, Jako C, Kumar A, Selvaraj G, Taylor DC (1999) The Arabidopsis thaliana TAG1 mutant has a mutation in a diacylglycerol acyltransferase gene. Plant J 19:645–653
Zweytick D, Athenstaedt K, Daum G (2000a) Intracellular lipid particles of eukaryotic cells. Biochim Biophys Acta 1469:101–120
Zweytick D, Leitner E, Kohlwein SD, Yu C, Rothblatt J, Daum G (2000b) Contribution of Are1p and Are2p to steryl ester synthesis in the yeast Saccharomyces cerevisiae. Eur J Biochem 267:1075–1082
Acknowledgements
Studies in our laboratories concerning TAG synthesis in yeast were financially supported by the Fonds zur Förderung der wissenschaftlichen Forschung in Österreich (project 15141) and the Austrian Ministry of Education, Science and Culture (project AUSTROFAN).
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Sorger, D., Daum, G. Triacylglycerol biosynthesis in yeast. Appl Microbiol Biotechnol 61, 289–299 (2003). https://doi.org/10.1007/s00253-002-1212-4
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DOI: https://doi.org/10.1007/s00253-002-1212-4