Mitochondrial inner membrane permeability changes induced by octadecadienoic acid hydroperoxide. Role of mitochondrial GSH pool.

The effect of exogenous octadecadienoic acid hydroperoxide (HPODE) on the functional properties of inner membrane of isolated rat liver mitochondria, as evaluated by the measurement of the membrane potential (delta psi) has been studied. Very low concentrations of HPODE (1.5-4.5 nmol/mg prot.) do not modify the delta psi of control mitochondria appreciably while bringing about the drop of delta psi, in a concentration-dependent mode, in mitochondria with a GSH level diminished by approx. 60%. Mitochondrial GSH depletion was obtained by intraperitoneal administration of buthionine sulfoximine, a specific inhibitor of GSH synthesis, to rats. The presence in the incubation system of GSH-methyl ester which normalizes mitochondrial GSH, fully prevents any drop in levels of delta psi induced by HPODE. The same protective effect has been presented by EGTA, which chelates the available Ca2+. Neither an antioxidant nor a specific inhibitor of mitochondrial phospholipase A2 are able to prevent the HPODE effect. From the results obtained we can assume that HPODE itself, at the concentrations used here, induces permeability changes in the inner membrane, with the loss of coupled functions, when the GSH mitochondrial level is below a critical value.