The involvement of the disulphide group of sporidesmin in the action of the toxin on swelling and respiration of liver mitochondria

The disulphide group of the mycotoxin sporidesmin appears to be involved in the action of the toxin on the swelling and increased respiration of mitochondria. The requirements of the swelling produced by sporidesmin and gliotoxin, a toxic antibiotic which also contains the epidithiapiperazinedione moiety, are similar. The swelling produced by oxidized glutathione is quite different as there is no requirement for substrate or phosphate and much higher concentrations of the disulphide are required. Dithiothreitol but not a number of mono- or other dithiols inhibits the action of 70 μM sporidesmin, 50 per cent reduction in the rate of swelling being observed at dithiothreitol concentrations of 42 μM. Dithiothreitol but not the other mono- and dithiols reacts with sporidesmin to form a number of products. It is suggested that effects of sporidesmin on mitochondria in vitro may involve a reaction between the disulphide group of the toxin and reactive thiols in the membrane and that sporidesmin may exert its primary effect in vivo by reacting with specific thiol groups of certain hepatic membranes.