Effect of oligomycin and succinate on mitochondrial metabolism of adenine nucleotides.

A decrease in the endogenous ATP of rat-liver mitochondria occurs in the presence of oligomycin. Such a decrease is enhanced by succinate and by arsenite, but not by α-ketoglutarate. In the presence of the latter, endogenous ATP actually increases. Exogenous ATP added to the mitochondria also undergoes a decrease upon incubation in the presence of oligomycin. Such a decrease is accompanied by a parallel increase in ADP and Pi. The ratio of Pi formed to ATP that has disappeared is significantly increased by succinate and even more by arsenite. In the presence of fluoride, PPi accumulates. From these experiments it is concluded that the presence of oligomycin makes apparent a rapid breakdown of ATP into AMP and PPi, which is normally masked by a concomitant synthesis due to the respiratory chain oxidative phosphorylation. It is proposed that succinate significantly enhances the disappearance both of endogenous and added ATP in the presence of oligomycin by inhibiting ATP formation via substrate-level phosphorylation linked to oxidation of endogenous α-ketoglutarate. © 1967.