Lonidamine-induced outer membrane permeability and susceptibility of mitochondria to inhibition by adriamycin.

Low concentrations of Adriamycin (ADM) do not inhibit the oxygen consumption of rat liver mitochondria because of the inability to cross the outer membrane. The involvement of this membrane as a permeability barrier is demonstrated by the results with exogenous ferrocytochrome c. ADM does not affect the basal rate of ferrocytochrome c oxidation, which, on the contrary, increases in Lonidamine (LND)-treated mitochondria. This difference lies in the capacity of LND to unmask the redox carriers in the inner membrane, i.e. cytochrome c:oxygen oxidoreductase which is also a marker of the outer membrane permeabilization. Therefore, the enhancement of ADM's effect on mitochondrial respiration by LND must be ascribed to its permeabilizing effect on the outer mitochondrial membrane.