AI Article Synopsis
- Etomoxir is a medicine that has been used for a long time to block a process called fatty acid β-oxidation in cells.
- Researchers found that etomoxir not only works on one specific protein called Cpt1 but also attaches to many other proteins involved in processing fatty acids in different parts of the cell.
- When they removed a protein called Pex5 that helps transport certain proteins into a part of the cell called the peroxisome, they discovered that etomoxir affected even more proteins, showing that it isn't a precise tool for studying fatty acid oxidation.
Article Abstract
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 . 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381838 | PMC |
| http://dx.doi.org/10.1016/j.isci.2024.110642 | DOI Listing |
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