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The Mammalian Malonyl-CoA Synthetase ACSF3 Is Required for Mitochondrial Protein Malonylation and Metabolic Efficiency

The Mammalian Malonyl-CoA Synthetase ACSF3 Is Required for Mitochondrial Protein Malonylation and Metabolic Efficiency

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BOWMAN, Caitlyn E., Susana RODRIGUEZ, Ebru S. SELEN ALPERGIN, Michelle G. ACOBA, Liang ZHAO, Thomas HARTUNG, Steven M. CLAYPOOL, Paul A. WATKINS, Michael J. WOLFGANG, 2017. The Mammalian Malonyl-CoA Synthetase ACSF3 Is Required for Mitochondrial Protein Malonylation and Metabolic Efficiency. In: Cell Chemical Biology. 24(6), pp. 673-684. ISSN 2451-9456. eISSN 2451-9456

@article{Bowman2017-06Mamma-39551, title={The Mammalian Malonyl-CoA Synthetase ACSF3 Is Required for Mitochondrial Protein Malonylation and Metabolic Efficiency}, year={2017}, doi={10.1016/j.chembiol.2017.04.009}, number={6}, volume={24}, issn={2451-9456}, journal={Cell Chemical Biology}, pages={673--684}, author={Bowman, Caitlyn E. and Rodriguez, Susana and Selen Alpergin, Ebru S. and Acoba, Michelle G. and Zhao, Liang and Hartung, Thomas and Claypool, Steven M. and Watkins, Paul A. and Wolfgang, Michael J.} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/39551"> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-07-11T09:11:37Z</dcterms:available> <dc:language>eng</dc:language> <dc:contributor>Bowman, Caitlyn E.</dc:contributor> <dc:creator>Selen Alpergin, Ebru S.</dc:creator> <dc:contributor>Selen Alpergin, Ebru S.</dc:contributor> <dc:creator>Hartung, Thomas</dc:creator> <dc:contributor>Claypool, Steven M.</dc:contributor> <dc:creator>Wolfgang, Michael J.</dc:creator> <dc:contributor>Zhao, Liang</dc:contributor> <dc:creator>Bowman, Caitlyn E.</dc:creator> <dc:contributor>Acoba, Michelle G.</dc:contributor> <dc:contributor>Hartung, Thomas</dc:contributor> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/39551"/> <dcterms:title>The Mammalian Malonyl-CoA Synthetase ACSF3 Is Required for Mitochondrial Protein Malonylation and Metabolic Efficiency</dcterms:title> <dc:contributor>Watkins, Paul A.</dc:contributor> <dc:creator>Rodriguez, Susana</dc:creator> <dc:creator>Claypool, Steven M.</dc:creator> <dcterms:issued>2017-06</dcterms:issued> <dcterms:abstract xml:lang="eng">Malonyl-coenzyme A (malonyl-CoA) is a central metabolite in mammalian fatty acid biochemistry generated and utilized in the cytoplasm; however, little is known about noncanonical organelle-specific malonyl-CoA metabolism. Intramitochondrial malonyl-CoA is generated by a malonyl-CoA synthetase, ACSF3, which produces malonyl-CoA from malonate, an endogenous competitive inhibitor of succinate dehydrogenase. To determine the metabolic requirement for mitochondrial malonyl-CoA, ACSF3 knockout (KO) cells were generated by CRISPR/Cas-mediated genome editing. ACSF3 KO cells exhibited elevated malonate and impaired mitochondrial metabolism. Unbiased and targeted metabolomics analysis of KO and control cells in the presence or absence of exogenous malonate revealed metabolic changes dependent on either malonate or malonyl-CoA. While ACSF3 was required for the metabolism and therefore detoxification of malonate, ACSF3-derived malonyl-CoA was specifically required for lysine malonylation of mitochondrial proteins. Together, these data describe an essential role for ACSF3 in dictating the metabolic fate of mitochondrial malonate and malonyl-CoA in mammalian metabolism.</dcterms:abstract> <dc:creator>Zhao, Liang</dc:creator> <dc:creator>Acoba, Michelle G.</dc:creator> <dc:contributor>Rodriguez, Susana</dc:contributor> <dc:creator>Watkins, Paul A.</dc:creator> <dc:contributor>Wolfgang, Michael J.</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2017-07-11T09:11:37Z</dc:date> </rdf:Description> </rdf:RDF>

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