Inhibition of electron transfer via the respiratory chain of fungal mitochondria by secondary plant metabolites

The effect of gossypol, quercetin, and scopoletin on the oxidation of vario us substrates by mitochondria and intact cells of the fungus Yarrowia lipol ytica was studied. Of the three plant metabolites studied, the triterpenoid aldehyde gossypol was the most potent inhibitor: this compound inhibited t he oxidation of exogenous NADH at a relatively low concentration (I-50 = 25 mu M). The oxidation of succinate and alpha-glycerophosphate was less sens itive to gossypol (I-50 for these substrates comprised 250 and 125 mu M, re spectively). The respiration of mitochondria was inhibited by the flavonoid quercetin and the coumaric compound scopoletin to a considerably lower deg ree than by gossypol, The I-50 constants of the inhibition of mitochondrial oxidation of NADH, succinate, and alpha-glycerophosphate by quercetin equa led 0.25, 0.4, and 0.3 mM, respectively. The constant of Inhibition of NADH and succinate oxidation by scopoletin was 6 mM. The data presented suggest that the fungicidal effect of gossypol and quercetin is due to the inhibit ion of electron transfer via the respiratory chain of mitochondria. Scopole tin probably has a different mechanism of action. A comparison of inhibitio n constants (I-50) during the, mitochondrial oxidation of various substrate s shows that gossypol selectively inhibits the dehydrogenase of exogenous N ADH.