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Monoacylglycerol Lipases Act as Evolutionarily Conserved Regulators of Non-oxidative Ethanol Metabolism
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Biochemistry and Molecular Biology
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882453/ https://www.ncbi.nlm.nih.gov/pubmed/27036938 http://dx.doi.org/10.1074/jbc.M115.705541 |
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author | Heier, Christoph Taschler, Ulrike Radulovic, Maja Aschauer, Philip Eichmann, Thomas O. Grond, Susanne Wolinski, Heimo Oberer, Monika Zechner, Rudolf Kohlwein, Sepp D. Zimmermann, Robert |
author_facet | Heier, Christoph Taschler, Ulrike Radulovic, Maja Aschauer, Philip Eichmann, Thomas O. Grond, Susanne Wolinski, Heimo Oberer, Monika Zechner, Rudolf Kohlwein, Sepp D. Zimmermann, Robert |
author_sort | Heier, Christoph |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4882453 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-48824532016-06-02 Monoacylglycerol Lipases Act as Evolutionarily Conserved Regulators of Non-oxidative Ethanol Metabolism Heier, Christoph Taschler, Ulrike Radulovic, Maja Aschauer, Philip Eichmann, Thomas O. Grond, Susanne Wolinski, Heimo Oberer, Monika Zechner, Rudolf Kohlwein, Sepp D. Zimmermann, Robert J Biol Chem Lipids 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. American Society for Biochemistry and Molecular Biology 2016-05-27 2016-03-31 /pmc/articles/PMC4882453/ /pubmed/27036938 http://dx.doi.org/10.1074/jbc.M115.705541 Text en © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) . |
spellingShingle | Lipids Heier, Christoph Taschler, Ulrike Radulovic, Maja Aschauer, Philip Eichmann, Thomas O. Grond, Susanne Wolinski, Heimo Oberer, Monika Zechner, Rudolf Kohlwein, Sepp D. Zimmermann, Robert Monoacylglycerol Lipases Act as Evolutionarily Conserved Regulators of Non-oxidative Ethanol Metabolism |
title | Monoacylglycerol Lipases Act as Evolutionarily Conserved Regulators of Non-oxidative Ethanol Metabolism |
title_full | Monoacylglycerol Lipases Act as Evolutionarily Conserved Regulators of Non-oxidative Ethanol Metabolism |
title_fullStr | Monoacylglycerol Lipases Act as Evolutionarily Conserved Regulators of Non-oxidative Ethanol Metabolism |
title_full_unstemmed | Monoacylglycerol Lipases Act as Evolutionarily Conserved Regulators of Non-oxidative Ethanol Metabolism |
title_short | Monoacylglycerol Lipases Act as Evolutionarily Conserved Regulators of Non-oxidative Ethanol Metabolism |
title_sort | monoacylglycerol lipases act as evolutionarily conserved regulators of non-oxidative ethanol metabolism |
topic | Lipids |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882453/ https://www.ncbi.nlm.nih.gov/pubmed/27036938 http://dx.doi.org/10.1074/jbc.M115.705541 |
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