title: Identification of Yju3p as functional orthologue of mammalian monoglyceride lipase in the yeast Saccharomycescerevisiae.
abstract: Monoacylglycerols (MAGs) are short-lived intermediates of glycerolipid metabolism. Specific molecular species, such as 2-arachidonoylglycerol, which is a potent activator of cannabinoid receptors, may also function as lipid signaling molecules. In mammals, enzymes hydrolyzing MAG to glycerol and fatty acids, resembling the final step in lipolysis, or esterifying MAG to diacylglycerol, are well known; however, despite the high level of conservation of lipolysis, the corresponding activities in yeast have not been characterized yet. Here we provide evidence that the protein Yju3p functions as a potent MAG hydrolase in yeast. Cellular MAG hydrolase activity was decreased by more than 90% in extracts of Yju3p-deficient cells, indicating that Yju3p accounts for the vast majority of this activity in yeast. Loss of this activity was restored by heterologous expression of murine monoglyceride lipase (MGL). Since yju3Delta mutants accumulated MAG in vivo only at very low concentrations, we considered the possibility that MAGs are re-esterified into DAG by acyltransferases. Indeed, cellular MAG levels were further increased in mutant cells lacking Yju3p and Dga1p or Lro1p acyltransferase activities. In conclusion, our studies suggest that catabolic and anabolic reactions affect cellular MAG levels. Yju3p is the functional orthologue of mammalian MGL and is required for efficient degradation of MAG in yeast.
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, A-8010 Graz, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Heier
authors.forename: Ulrike
authors.initials: U
authors.lastname: Taschler
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Rengachari
authors.forename: Monika
authors.initials: M
authors.lastname: Oberer
authors.forename: Heimo
authors.initials: H
authors.lastname: Wolinski
authors.forename: Klaus
authors.initials: K
authors.lastname: Natter
authors.forename: Sepp D
authors.initials: SD
authors.lastname: Kohlwein
authors.forename: Regina
authors.initials: R
authors.lastname: Leber
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmermann
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D005816:Genetic Complementation Test; D006868:Hydrolysis; D051379:Mice; D008969:Molecular Sequence Data; D008994:Monoacylglycerol Lipases / Q000235:genetics / Q000378:metabolism*; D050178:Monoglycerides / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D014280:Triglycerides / Q000378:metabolism
chemical_list: D050178:Monoglycerides; D029701:Saccharomyces cerevisiae Proteins; D014280:Triglycerides; D000217:Acyltransferases; C494880:DGA1 protein, S cerevisiae; D051048:Diacylglycerol O-Acyltransferase; D008994:Monoacylglycerol Lipases; C552818:Yju3 protein, S cerevisiae