<i>ROG1</i> encodes a monoacylglycerol lipase in <i>Saccharomyces cerevisiae</i>

Varthini, Lakshmanaperumal Vishnu; Kandasamy, Selvaraju; Srinivasan, Malathi; Nachiappan, Vasanthi

doi:10.1016/j.febslet.2014.11.019

Cited by 8 publications

(4 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result highlights the role of Ser 207 in forming covalent bonding with the substrates and its importance in the activity of lipases with conserved GXSXG motif. These observations correlate with the in vitro mutational studies of lipases, MGAT of Arachis hypogaea [ 37 ] Cvt17 [ 38 ] Lpl1 [ 39 ], ROG1 [ 40 ] of S. cerevisiae which showed no or marginal activity when serine of GXSXG motif was mutated with alanine.…”

Section: Resultssupporting

confidence: 73%

Molecular characterization of human ABHD2 as TAG lipase and ester hydrolase

et al. 2016

View full text Add to dashboard Cite

Alterations in lipid metabolism have been progressively documented as a characteristic property of cancer cells. Though, human ABHD2 gene was found to be highly expressed in breast and lung cancers, its biochemical functionality is yet uncharacterized. In the present study we report, human ABHD2 as triacylglycerol (TAG) lipase along with ester hydrolysing capacity. Sequence analysis of ABHD2 revealed the presence of conserved motifs G205XS207XG209 and H120XXXXD125. Phylogenetic analysis showed homology to known lipases, Drosophila melanogaster CG3488. To evaluate the biochemical role, recombinant ABHD2 was expressed in Saccharomyces cerevisiae using pYES2/CT vector and His-tag purified protein showed TAG lipase activity. Ester hydrolase activity was confirmed with pNP acetate, butyrate and palmitate substrates respectively. Further, the ABHD2 homology model was built and the modelled protein was analysed based on the RMSD and root mean square fluctuation (RMSF) of the 100 ns simulation trajectory. Docking the acetate, butyrate and palmitate ligands with the model confirmed covalent binding of ligands with the Ser207 of the GXSXG motif. The model was validated with a mutant ABHD2 developed with alanine in place of Ser207 and the docking studies revealed loss of interaction between selected ligands and the mutant protein active site. Based on the above results, human ABHD2 was identified as a novel TAG lipase and ester hydrolase.

show abstract

Section: Resultssupporting

confidence: 73%

Molecular characterization of human ABHD2 as TAG lipase and ester hydrolase

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Interestingly, they do retain their activity as lysophospholipid acyltransferases in contrast with Tgl3 , however, the biological relevance of this activity in the ER remains to be determined. Yju3, Rog1, and Mgl2 are the monoacylglycerol (MAG) lipases, generating a free fatty acid and glycerol as the ultimate step in TAG hydrolysis, and are predominantly associated with membranes and lipid droplets . The mobilization of SE is catalyzed by three partially functionally redundant lipases, Tgl1, Yeh1, and Yeh2 (Fig.…”

Section: Lipid Droplet Mobilizationmentioning

confidence: 99%

Lipid droplet‐mediated lipid and protein homeostasis in budding yeast

Graef

2018

FEBS Letters

View full text Add to dashboard Cite

Lipid droplets are conserved specialized organelles that store neutral lipids. Our view on this unique organelle has evolved from a simple fat deposit to a highly dynamic and functionally diverse hub—one that mediates the buffering of fatty acid stress and the adaptive reshaping of lipid metabolism to promote membrane and organelle homeostasis and the integrity of central proteostasis pathways, including autophagy, which ensure stress resistance and cell survival. This Review will summarize the recent developments in the budding yeast Saccharomyces cerevisiae, as this model organism has been instrumental in deciphering the fundamental mechanisms and principles of lipid droplet biology and interconnecting lipid droplets with many unanticipated cellular functions applicable to many other cell systems.

show abstract

“…2 E ). To test if Rog1p, a second MAG lipase in yeast ( 49 ), harbors FAEE hydrolase activity we expressed the enzyme in WT and yju3 Δ cells and performed hydrolase assays. ROG1 expression moderately increased MAG hydrolase activity in yju3 Δ but not in WT homogenates ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Monoacylglycerol Lipases Act as Evolutionarily Conserved Regulators of Non-oxidative Ethanol Metabolism

Heier

Taschler

Radulovic

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Fatty acid ethyl esters (FAEEs) are non-oxidative metabolites of ethanol that accumulate in human tissues upon ethanol intake. Although FAEEs are considered as toxic metabolites causing cellular dysfunction and tissue damage, the enzymology of FAEE metabolism remains poorly understood. In this study, we used a biochemical screen in Saccharomyces cerevisiae to identify and characterize putative hydrolases involved in FAEE catabolism. We found that Yju3p, the functional orthologue of mammalian monoacylglycerol lipase (MGL), contributes >90% of cellular FAEE hydrolase activity, and its loss leads to the accumulation of FAEE. Heterologous expression of mammalian MGL in yju3Δ mutants restored cellular FAEE hydrolase activity and FAEE catabolism. Moreover, overexpression or pharmacological inhibition of MGL in mouse AML-12 hepatocytes decreased or increased FAEE levels, respectively. FAEEs were transiently incorporated into lipid droplets (LDs) and both Yju3p and MGL co-localized with these organelles. We conclude that the storage of FAEE in inert LDs and their mobilization by LD-resident FAEE hydrolases facilitate a controlled metabolism of these potentially toxic lipid metabolites.

show abstract

ROG1 encodes a monoacylglycerol lipase in Saccharomyces cerevisiae

Cited by 8 publications

References 25 publications

Molecular characterization of human ABHD2 as TAG lipase and ester hydrolase

Molecular characterization of human ABHD2 as TAG lipase and ester hydrolase

Lipid droplet‐mediated lipid and protein homeostasis in budding yeast

Monoacylglycerol Lipases Act as Evolutionarily Conserved Regulators of Non-oxidative Ethanol Metabolism

Contact Info

Product

Resources

About