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Etomoxir: A Promiscuous Fatty Acid Mimetic Chemoproteomic Probe

ABSTRACT: Etomoxir has been used for decades as a popular small molecule inhibitor of Carnitine Palmitoyltransferase I, Cpt1, to block mitochondrial fatty acid b-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. The loss of Pex5, required for the import of peroxisomal matrix proteins, eliminated many of these proteins. By utilizing the promiscuous, covalent and fatty acid mimetic properties of etomoxir, novel etomoxir targets of fatty acid w-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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Primary Cell, Hepatocyte

SUBMITTER: Michael Wolfgang

LAB HEAD: Michael J. Wolfgang

PROVIDER: PXD051969 | Pride | 2024-05-04

REPOSITORIES: Pride

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			Action	DRS
	PrimaryHepatocytes_MBR_CHYMERYS_LFQ.sld	Other
	RO_CS_481_240404_WolfgangM_MW_3Conditions4Reps_LFQ_CHIMERYS_DDA.mgf	Mgf
	RO_CS_481_240404_WolfgangM_MW_3Conditions4Reps_LFQ_CHIMERYS_DDA.mzML	Mzml
	RO_CS_481_240404_WolfgangM_MW_3Conditions4Reps_LFQ_CHIMERYS_DDA.mzid.gz	Mzid
	RO_CS_481_240404_WolfgangM_MW_Alk1.raw	Raw

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Etomoxir as a Promiscuous Chemoproteomic Probe.

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