title: Obese yeast: triglyceride lipolysis is functionally conserved from mammals to yeast.
abstract: Storage and degradation of triglycerides are essential processes to ensure energy homeostasis and availability of precursors for membrane lipid synthesis. Recent evidence suggests that an emerging class of enzymes containing a conserved patatin domain are centrally important players in lipid degradation. Here we describe the identification and characterization of a major triglyceride lipase of the adipose triglyceride lipase/Brummer family, Tgl4, in the yeast Saccharomyces cerevisiae. Elimination of Tgl4 in a tgl3 background led to fat yeast, rendering growing cells unable to degrade triglycerides. Tgl4 and Tgl3 lipases localized to lipid droplets, independent of each other. Serine 315 in the GXSXG lipase active site consensus sequence of the patatin domain of Tgl4 is essential for catalytic activity. Mouse adipose triglyceride lipase (which also contains a patatin domain but is otherwise highly divergent in primary structure from any yeast protein) localized to lipid droplets when expressed in yeast, and significantly restored triglyceride breakdown in tgl4 mutants in vivo. Our data identify yeast Tgl4 as a functional ortholog of mammalian adipose triglyceride lipase.
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Schubertstrasse 1, A8010 Graz, Austria.
authors.forename: Christoph F
authors.initials: CF
authors.lastname: Kurat
authors.forename: Klaus
authors.initials: K
authors.lastname: Natter
authors.forename: Julia
authors.initials: J
authors.lastname: Petschnigg
authors.forename: Heimo
authors.initials: H
authors.lastname: Wolinski
authors.forename: Kim
authors.initials: K
authors.lastname: Scheuringer
authors.forename: Harald
authors.initials: H
authors.lastname: Scholz
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Regina
authors.initials: R
authors.lastname: Leber
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
authors.forename: Sepp D
authors.initials: SD
authors.lastname: Kohlwein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D004075:Diglycerides / Q000378:metabolism; D019143:Evolution, Molecular; D007700:Kinetics; D008049:Lipase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008066:Lipolysis / Q000502:physiology*; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009765:Obesity / Q000201:enzymology; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D013379:Substrate Specificity; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D004075:Diglycerides; D029701:Saccharomyces cerevisiae Proteins; D014280:Triglycerides; D008049:Lipase; C476342:TGL3 protein, S cerevisiae; C506904:Tgl4 protein, S cerevisiae; C506905:Tgl5 protein, S cerevisiae