The effects of demethylsterigmatocystin and sterigmatin on ATP synthesis system in mitochondria: A comparison with sterigmatocystin.

The effects of demethylsterigmatocystin and its structural isomer, sterigmatin, on oxidative phosphorylation of mitochondria were studied by means of isolated rat liver mitochondria in comparison with sterigmatocystin. Both compounds were found to uncouple the oxidative phosphorylation in mitochondria, causing marked decreases in RC index and P/O ratio. Sterigmatin, in which dihydrobisfuran ring and xanthone nucleus are combined in a linear manner, was evidently more toxic to mitochondrial functions than demethylsterigmatocystin which was an angular molecular shape. Though their uncoupling concentrations were rather high for assessing theirin vivo toxicity, a good correspond was observed between their orders of potencies in the toxicity to mitochondrial functions and in the cytotoxicity to rat hepatocytes. The demethylation of sterigmatocystin resulted in an obvious decrease of uncoupling activity.