Vishal M Gohil, Lin Zhu, Charli D Baker, Valentin Cracan, Abbas Yaseen, Mohit Jain, Clary B Clish, Paul S Brookes, Marica Bakovic, Vamsi K Mootha
We recently identified meclizine, an over-the-counter drug, as an inhibitor of mitochondrial respiration. Curiously, meclizine blunted respiration in intact cells but not in isolated mitochondria, suggesting an unorthodox mechanism. Using a metabolic profiling approach, we now show that treatment with meclizine leads to a sharp elevation of cellular phosphoethanolamine, an intermediate in the ethanolamine branch of the Kennedy pathway of phosphatidylethanolamine biosynthesis. Metabolic labeling and in vitro enzyme assays confirmed direct inhibition of the cytosolic enzyme CTP:phosphoethanolamine cytidylyltransferase (PCYT2)...
December 6, 2013: Journal of Biological Chemistry