Effect of diphtheria toxin fragment A on energy coupling in mitochondria. Studies on mouse liver mitoplasts

Abstract

The effect of intact diphtheria toxin and of its fragment A on protein synthesis in mouse liver mitoplasts (digitonin-treated mitochondria) was studied. Frag- ment A inhibited protein synthesis in intact mitoplasts to the same extent as the un- coupler, carbonylcyanide p-trifluoromethoxyphenylhydrazone, but similar effects were not observed in lyzed mitoplasts. Intact diphtheria toxin was without effect in either case. Fragment A strongly stimulated mitochondrial ATPase activity. At concentrations which efficiently inhibited mitochondrial protein synthesis and stimulated ATPase activity, fragment A had no effect on the intramitochondrial concentration of nicotin- amide adenine dinucleotides. Moreover, it did not catalyze ADP ribosylation of mito- chondrial proteins. The results indicate that the effects observed did not involve the NAD + -glycohydrolase activity of fragment A.