Site of impairment of oxidative phosphorylation in irradiated rats

Abstract

There is a significant inhibition of liver mitochondrial oxidative phosphorylation at 72 h following whole-body X-irradiation of rats with a dose of 800 rad. The three sites of phosphorylation coupled to electron transport show differential sensitivities to radiation, the terminal site being far more affected than the other two. Studies on NAD⁺ reduction by reversal of electron flow, with the energy for the process being derived from the oxidation of ascorbate-tetramethyl-ρ-phenylenediamine, suggest that the formation of high-energy intermediates is not interfered with by irradiation. On the other hand, there is 2-fold evidence in favour of an impairment of the transphosphorylation function. Thus, by reconstitution studies, the activity of coupling factor F₁ is found to be greatly decreased in irradiated rat livers. With ATP as an energy source, phosphorylating submitochondrial particles from livers of irradiated rats show a lower rate of reduction of NAD⁺. The site-specificity of the radiation effect is discussed in relation to current concepts of oxidative phosphorylation.