Toxicity of emestrin, a new macrocyclic dithiodioxopiperazine mycotoxin, to mitochondrial function.

The effect of emestrin, a new macrocyclic epidithiodioxopiperazine mycotoxin from severalEmericella species, on mitochondrial reactions was studied using isolated rat liver mitochondria to gain insight into the molecular mechanism for itsin vivo toxicity to rat and mouse. Emestrin was found to inhibit ATP synthesis in mitochondria causing an uncoupling of oxidative phosphorylation and a depression of respiration in isolated mitochondria. In addition to these effects on mitochondrial respiration, emestrin elicited a dratsic structural alteration (swelling) of mitochondria as observed in thein vivo system. The mitochondrial swelling was significantly enhanced by the subsequent addition of calcium ion. Emestrin B, in which dithio group is replaced by trithio group, exerted an uncoupling effect on oxidative phosphorylation without accompanying such depressive effect on state 3 respiration as observed for emestrin.