• Torgeir Flatmark

      Articles written in Journal of Biosciences

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

      Abraham K Abraham Torgeir Flatmark Alexander Pihl Anni Vedeler

      More Details Abstract Fulltext PDF

      The effect of intact diphtheria toxin and of its fragment A on protein synthesis in mouse liver mitoplasts (digitonin-treated mitochondria) was studied. Fragment A inhibited protein synthesis in intact mitoplasts to the same extent as the uncoupler, carbonylcyanidep-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 mitochondrial proteins. The results indicate that the effects observed did not involve the NAD+-glycohydrolase activity of fragment A.

      [125I]-Labelled fragment A was bound to mitoplasts to about the same extent as the labelled intact diphtheria toxin.

      The present results suggest that fragment A of diphtheria toxin is capable of inhibiting the energy coupling in mitoplasts, thereby inhibiting protein synthesis. The detailed mechanism of the uncoupling and its possible physiological significance remains to be elucidated

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