YMR313c/TGL3 Encodes a Novel Triacylglycerol Lipase Located in Lipid Particles of Saccharomyces cerevisiae

Athenstaedt, Karin; Daum, Güenther

doi:10.1074/jbc.m302577200

Cited by 191 publications

(171 citation statements)

References 42 publications

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“…The observed prevalent turnover of unsaturated TG species is consistent with the described in vitro specificity of the yeast TG lipases (12,42). As expected and consistent with previous observations (4,12,42), tgl3 tgl4 mutants had about threefold elevated TG levels ( Fig. 2B and Fig.…”

Section: Lipolysis-defective Mutants Accumulate Saturated and Unsatursupporting

confidence: 79%

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

Chauhan

Visram

Cristobal-Sarramian

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Cell growth and division requires the precise duplication of cellular DNA content but also of membranes and organelles. Knowledge about the cell-cycle-dependent regulation of membrane and storage lipid homeostasis is only rudimentary. Previous work from our laboratory has shown that the breakdown of triacylglycerols (TGs) is regulated in a cell-cycle-dependent manner, by activation of the Tgl4 lipase by the major cyclin-dependent kinase Cdc28. The lipases Tgl3 and Tgl4 are required for efficient cell-cycle progression during the G1/S (Gap1/replication phase) transition, at the onset of bud formation, and their absence leads to a cell-cycle delay. We now show that defective lipolysis activates the Swe1 morphogenesis checkpoint kinase that halts cell-cycle progression by phosphorylation of Cdc28 at tyrosine residue 19. Saturated longchain fatty acids and phytosphingosine supplementation rescue the cell-cycle delay in the Tgl3/Tgl4 lipase-deficient strain, suggesting that Swe1 activity responds to imbalanced sphingolipid metabolism, in the absence of TG degradation. We propose a model by which TG-derived sphingolipids are required to activate the protein phosphatase 2A (PP2A Cdc55 ) to attenuate Swe1 phosphorylation and its inhibitory effect on Cdc28 at the G1/S transition of the cell cycle.T he eukaryotic cell cycle is a highly coordinated and conserved process. In addition to DNA replication, one of the major requirements for the cell to progress through the cell cycle is the precise duplication of membrane-enclosed organelles and other cellular components before cell division. Knowledge about the mechanisms regulating (membrane) lipid homeostasis during the cell cycle is scarce (1), however several levels of evidence suggest regulation of key enzymes of lipid metabolism in a cell-cycledependent manner. The PAH1-encoded phosphatidic acid (PA) phosphatase (Pah1), a key enzyme of triacylglycerol (TG) synthesis that provides the TG precursor diacylglycerol (DG), is phosphorylated and inactivated by the cyclin-dependent kinases Cdc28 and Pho85-Pho80 (2, 3). Kurat et al. showed that Tgl4, next to Tgl3, one of the two major TG lipases in yeast and the ortholog of mammalian ATGL (4, 5), is also phosphorylated by Cdc28. In contrast to Pah1, however, Tgl4 is activated by Cdc28 (6). This inverse regulation of Pah1 and Tgl4 by Cdc28-dependent phosphorylation led to the model by which the TG content oscillates during the cell cycle: On the one hand, TG synthesis serves as a buffer for excess de novo generated fatty acids (FAs), and on the other hand, in times of increased demand-that is, at the onset of bud formation and bud growth-Tgl4-catalyzed lipolysis becomes active to provide TG-derived precursors for membrane lipid synthesis (6).TG and membrane phospholipids share the same intermediates, PA and DG; PA is generated by sequential acylation of glycerol-3-phosphate, reactions that mostly take place in the endoplasmic reticulum (ER) membrane (7). The dephosphorylation of PA to DG by the PAH1-encoded PA phosphatase Pah1 is ...

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Section: Lipolysis-defective Mutants Accumulate Saturated and Unsatursupporting

confidence: 79%

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

Chauhan

Visram

Cristobal-Sarramian

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…In the wild type background, GFP-Tgl3p was located to LD (Fig. 2B) and co-localized with Nile Red confirming previous results from our laboratory (20). In the QM, GFP-Tgl3p was enriched in the nuclear ER exhibiting co-localization with the ER marker protein Sec61-mCherry.…”

Section: Lack Of Nonpolar Lipids Affects Gene Expression Proteinsupporting

confidence: 78%

“…3 However, smaller amounts of Tgl3-Myc were also detected in 30,000 ϫ g (M30) and 40,000 ϫ g microsomes (M40) from wild type cells. This result is in contrast to previous studies (20) where a less sensitive assay system did not detect Tgl3p in microsomes. Thus, results presented here demonstrate that Tgl3p also belongs to the group of proteins that are dually located to LD and the ER.…”

Section: Lack Of Nonpolar Lipids Affects Gene Expression Proteincontrasting

confidence: 56%

Regulation of the Yeast Triacylglycerol Lipase Tgl3p by Formation of Nonpolar Lipids

Schmidt

Athenstaedt

Koch

et al. 2013

Journal of Biological Chemistry

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Background: Tgl3p from yeast serves as the major triacylglycerol lipase but also as lysophospholipid acyltransferase. Results: Formation of nonpolar lipids strongly affects subcellular localization and function of Tgl3p. Conclusion: Tgl3p activity is mainly regulated by the presence/absence of lipid droplets. Significance: The yeast lipase/acyltransferase Tgl3p is an important player in lipid homeostasis.

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“…It came as a surprise that such an enzyme was not associated with lipid particles, the site of STE storage and the obvious starting point for STE mobilization. A related process, the mobilization of TAG from lipid particles, was recently shown to be catalyzed by the lipid particle located Tgl3p, the major TAG lipase of S. cerevisiae (43). On the other hand, the mammalian hormone sensitive lipase HSL, which catalyzes hydrolysis of TAG, diacylglycerols, monoacylglycerols, lipoidal, and retinyl esters and also cholesteryl esters (44 -46), is a cytosolic protein under basal conditions.…”

Section: Discussionmentioning

confidence: 99%

YEH2/YLR020c Encodes a Novel Steryl Ester Hydrolase of the Yeast Saccharomyces cerevisiae

Müllner

Deutsch

Leitner

et al. 2005

Journal of Biological Chemistry

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Previous work from our laboratory (Zinser, E., Paltauf, F., and Daum, G. (1993) J. Bacteriol. 175, 2853-2858) demonstrated steryl ester hydrolase activity in the plasma membrane of the yeast Saccharomyces cerevisiae. Here, we show that the gene product of YEH2/ YLR020c, which is homologous to several known mammalian steryl ester hydrolases, is the enzyme catalyzing this reaction. Deletion of yeast YEH2 led to complete loss of plasma membrane steryl ester hydrolase activity whereas overexpression of the gene resulted in a significant elevation of the activity. Purification of enzymatically active Yeh2p close to homogeneity unambiguously identified this protein as a steryl ester hydrolase and thus as the first enzyme of this kind characterized in S. cerevisiae. In addition to evidence obtained in vitro experiments in vivo contributed to the characterization of this novel enzyme. Sterol analysis of yeh2⌬ unveiled a slightly elevated level of zymosterol suggesting that the esterified form of this sterol precursor is a preferred substrate of Yeh2p. However, in strains bearing hybrid proteins with strongly enhanced Yeh2p activity decreased levels of all steryl esters were observed. Thus, it appears that Yeh2p activity is not restricted to distinct steryl esters but rather has broad substrate specificity. The fact that in a yeh2⌬ deletion strain bulk steryl ester mobilization occurred at a similar rate as in wild type suggested that Yeh2p is not the only steryl ester hydrolase but that other enzymes with overlapping function exist in the yeast.Most eukaryotic cells contain and synthesize sterols, which are essential lipid components of membranes. Besides their role in maintaining membrane permeability and fluidity, effects of sterols on aerobic metabolism (1, 2), completion of the cell cycle (3) as well as on sterol uptake (4) and sterol transport (5) have been described. Considering the different functions of sterols it is obvious that sterol homeostasis, including sterol biosynthesis, uptake, transport, storage, utilization, and efflux, has to be a strictly regulated process. Specific sterols present in different eukaryotic cells vary, ergosterol being the major sterol in the yeast Saccharomyces cerevisiae.Besides other regulatory mechanisms esterification of sterols and hydrolysis of steryl esters (STE) 1 play an important role in cellular sterol homeostasis. These processes do not only allow cells to store chemical energy, which can be used in times of deprivation, but also provide an additional means to balance the concentrations of free sterols and fatty acids, which are essential and critical for cell structure and function. In mammalian cells esterification of sterols is catalyzed either by lecithin:cholesteryl acyltransferase (reviewed in Refs. 6 -8) or by the two acyl-CoA:cholesteryl acyltransferases ACAT1 and ACAT2 (reviewed in Ref. 9). Cholesteryl ester hydrolysis occurs by a number of mammalian enzymes many of which have already been identified, among them carboxyl ester lipase (CEL), lysosomal acid lipase...

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YMR313c/TGL3 Encodes a Novel Triacylglycerol Lipase Located in Lipid Particles of Saccharomyces cerevisiae

Cited by 191 publications

References 42 publications

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

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

Regulation of the Yeast Triacylglycerol Lipase Tgl3p by Formation of Nonpolar Lipids

YEH2/YLR020c Encodes a Novel Steryl Ester Hydrolase of the Yeast Saccharomyces cerevisiae

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