Inhibition of mitochondrial translation by calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide

The possible role of calmodulin in mitochondrial functions was investigated in Ehrlich ascites tumor cell and mouse liver mitochondria employing sulfonamide compounds as calmodulin indicators. N-[6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7), the most potent of the sulfonamide compounds, inhibited mitochondrial protein synthesis and oxidative phosphorylation. The inhibitors had no significant effect on mitochondrial cytochrome c oxidase, oligomycin-sensitive ATPase and NADH dehydrogenase activities. Depletion of endogenous ATP pool seemed to be the main mechanism of inhibition of mitochondrial translation by sulfonamides. The results also show that mitochondria from hepatic tissues are relatively less sensitive to sulfonamide drugs as compared to the Ehrlich ascites tumor cell mitochondria. Results of Ca²⁺ autoradiography revealed 2-3-fold higher levels of calmodulin-like Ca²⁺ binding protein in extracts from Ehrlich ascites tumor cell mitoplasts as compared to mitoplasts from mouse liver. These results suggest cell and tissue specific variations in Ca²⁺-dependent processes in the mitochondrial compartment.