Intramitochondrial fatty acid activation enhances control strength of adenine nucleotide translocase

In incubations with isolated rat liver mitochondria we studied the fuel properties of octanoate as medium-chain fatty acid and respiratory substrate and the extent of control exerted by adenine nucleotide translocase on mitochondrial respiration. While, compared with pyruvate, octanoate improved the hydrogen supply in the active state to be seen from a high reduction of the mitochondrial NAD(P) system and an increased delta psi, it also decreased the efficiency of energy transduction indicated by a low ADP/O ratio. Based on measurements of the dependence of respiration on the extramitochondrial ATP/ADP ratio, we conclude that a switch-over from pyruvate to fatty acid oxidation does not change the kinetic parameters which make respiration respond to the ATP/ADP ratio. It is shown that the decrease of the exchangeable intramitochondrial adenine nucleotide pool due to the activation of octanoate results in a decrease of the activity of the adenine nucleotide translocase and an increase of its flux control coefficient.