Publications

• MGL2/YMR210w encodes a monoacylglycerol lipase in Saccharomyces cerevisiae.

  Selvaraju K., Gowsalya R., Vijayakumar R., Nachiappan V.

  In silico analysis of the uncharacterized open reading frame YMR210w in Saccharomyces cerevisiae revealed that it possesses both an α/β hydrolase domain (ABHD) and a typical lipase (GXSXG) motif. The purified protein displayed monoacylglycerol (MAG) lipase activity and preferred palmitoyl-MAG. Ove ... >> More

  In silico analysis of the uncharacterized open reading frame YMR210w in Saccharomyces cerevisiae revealed that it possesses both an α/β hydrolase domain (ABHD) and a typical lipase (GXSXG) motif. The purified protein displayed monoacylglycerol (MAG) lipase activity and preferred palmitoyl-MAG. Overexpression of YMR210w in the known MAG lipase mutant yju3Δ clearly revealed that the protein had MAG lipase activity, hence we named the ORF MGL2. Overexpression of YMR210w decreased the cellular triacylglycerol levels. Analysis of the overexpressed strains showed reduction in the lipid droplets number and size. Phenotype studies revealed that the double deletion yju3Δmgl2Δ displayed a growth defect that was partially restored by MGL2 overexpression. << Less

  FEBS Lett. 590:1174-1186(2016) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Biochemical characterization of the PHARC-associated serine hydrolase ABHD12 reveals its preference for very-long-chain lipids.

  Joshi A., Shaikh M., Singh S., Rajendran A., Mhetre A., Kamat S.S.

  Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a rare genetic human neurological disorder caused by null mutations to the <i>Abhd12</i> gene, which encodes the integral membrane serine hydrolase enzyme ABHD12. Although the role that ABHD12 plays in PHARC is und ... >> More

  Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a rare genetic human neurological disorder caused by null mutations to the <i>Abhd12</i> gene, which encodes the integral membrane serine hydrolase enzyme ABHD12. Although the role that ABHD12 plays in PHARC is understood, the thorough biochemical characterization of ABHD12 is lacking. Here, we report the facile synthesis of mono-1-(fatty)acyl-glycerol lipids of varying chain lengths and unsaturation and use this lipid substrate library to biochemically characterize recombinant mammalian ABHD12. The substrate profiling study for ABHD12 suggested that this enzyme requires glycosylation for optimal activity and that it has a strong preference for very-long-chain lipid substrates. We further validated this substrate profile against brain membrane lysates generated from WT and ABHD12 knockout mice. Finally, using cellular organelle fractionation and immunofluorescence assays, we show that mammalian ABHD12 is enriched on the endoplasmic reticulum membrane, where most of the very-long-chain fatty acids are biosynthesized in cells. Taken together, our findings provide a biochemical explanation for why very-long-chain lipids (such as lysophosphatidylserine lipids) accumulate in the brains of ABHD12 knockout mice, which is a murine model of PHARC. << Less

  J. Biol. Chem. 293:16953-16963(2018) [PubMed] [EuropePMC]

  This publication is cited by 17 other entries.

• Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis.

  Nomura D.K., Long J.Z., Niessen S., Hoover H.S., Ng S.W., Cravatt B.F.

  Tumor cells display progressive changes in metabolism that correlate with malignancy, including development of a lipogenic phenotype. How stored fats are liberated and remodeled to support cancer pathogenesis, however, remains unknown. Here, we show that the enzyme monoacylglycerol lipase (MAGL) i ... >> More

  Tumor cells display progressive changes in metabolism that correlate with malignancy, including development of a lipogenic phenotype. How stored fats are liberated and remodeled to support cancer pathogenesis, however, remains unknown. Here, we show that the enzyme monoacylglycerol lipase (MAGL) is highly expressed in aggressive human cancer cells and primary tumors, where it regulates a fatty acid network enriched in oncogenic signaling lipids that promotes migration, invasion, survival, and in vivo tumor growth. Overexpression of MAGL in nonaggressive cancer cells recapitulates this fatty acid network and increases their pathogenicity-phenotypes that are reversed by an MAGL inhibitor. Impairments in MAGL-dependent tumor growth are rescued by a high-fat diet, indicating that exogenous sources of fatty acids can contribute to malignancy in cancers lacking MAGL activity. Together, these findings reveal how cancer cells can co-opt a lipolytic enzyme to translate their lipogenic state into an array of protumorigenic signals. PAPERFLICK: << Less

  Cell 140:49-61(2010) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.