Calmodulin antagonists inhibit the mitochondrial pyruvate dehydrogenase complex

Calmodulin antagonists, including phenothiazine, sulfonamide, butyrophenone, and imidazolium derivatives, were in vitro inhibitors of pea mitochondrial pyruvate dehydrogenase complex activity. Inhibition was observed both during direct assay of the partially purified complex and during assay of pyruvate oxidation by isolated, intact mitochondria. When tested against the purified complex, the sulfonamide compound N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) was a competitive inhibitor with respect to coenzyme A and an uncompetitive inhibitor with respect to NAD and pyruvate. Inhibition of a process as crucial as mitochondrial respiration should serve to emphasize the care necessary in interpretation of whole-organism calmodulin antagonist studies.