Inhibition of mitochondrial respiration by chalepin, a naturally occurring furocoumarin.

Polarographic measurements of the rates of oxygen consumption by isolated rat liver mitochondria respiring on pyruvate/malate in metabolic state 4 revealed that additions of micromolar amounts of chalepin, a naturally occurring furocoumarin resulted in significant decreases in respiratory rates. At 16 microM chalepin, respiration was inhibited by at least 40%. A maximum inhibition of 60% was obtained at 80 microM chalepin. Whereas 16 microM chalepin gave 76% reduction of respiratory control ratio, at most 80% reduction was obtained at greater than or equal to 80 microM chalepin. There was no significant effect on either metabolic state 4 respiration or respiratory control ratio when succinate was used as electron donor. A comparison with the effects of rotenone indicates that chalepin is probably only one-tenth as potent as this classical inhibitor of respiration. These results show that chalepin-like rotenone is an inhibitor of energy coupling site 1.