Etomoxir repurposed as a promiscuous fatty acid mimetic chemoproteomic probe.

Autor:	Choi J; Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Smith DM; Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Lee YJ; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Cai D; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Hossain MJ; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., O'Connor TJ; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Deme P; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Haughey NJ; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Scafidi S; Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Riddle RC; Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD, USA.; Research and Development Service, Baltimore VA Medical Center, Baltimore, MD, USA., Wolfgang MJ; Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2024 Aug 02; Vol. 27 (9), pp. 110642. Date of Electronic Publication: 2024 Aug 02 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.110642
Abstrakt:	Etomoxir has been used for decades as a popular small molecule inhibitor of carnitine palmitoyltransferase I, Cpt1, to block mitochondrial fatty acid β-oxidation. To test the specificity of etomoxir, we generated click chemistry-enabled reagents to label etomoxir binding proteins in situ . Etomoxir bound to Cpt1, but also bound to a large array of diverse proteins that metabolize and transport fatty acids in the cytoplasm, peroxisome, and mitochondria. Many of the most abundant proteins identified in primary hepatocytes were peroxisomal proteins. The loss of Pex5, required for the import of peroxisomal matrix proteins, eliminated many of these etomoxir-labeled proteins. By utilizing the promiscuous, covalent, and fatty acid mimetic properties of etomoxir, etomoxir targets of fatty acid ω-oxidation were revealed following the loss of Pex5. These data demonstrate that etomoxir is not specific for Cpt1 and is not appropriate as a tool to distinguish the biological effects of fatty acid oxidation. Competing Interests: The authors declare no competing interests. (© 2024 The Author(s).)
Databáze:	MEDLINE
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