Abolition by 2 : 4-Dinitrophenol of the Protective Effect of Succinate and Adenine Nucleotides on the Onset of the Thyroxine-induced Swelling of Liver Mitochondria

Abstract

THYROXINE is known^1,2 to induce a rapid and extensive swelling of freshly isolated rat and mouse liver mitochondria suspended in a deficient medium. It has been reported recently³ that succinate (5 × 10⁻⁴ M) and adenine nucleotides (10⁻⁵ M) protect against the onset of this swelling for a certain time, but not against the extent of swelling ultimately reached. The former effect was very pronounced with liver mitochondria from rats maintained on a polished-rice diet for 3–12 months. These experiments were carried out with inbred albino rats of the strain R-Amsterdam and F ₂ (C57 Black × CBA) hybrid mice. It has now been found that the protective effect is weaker when liver mitochondria from several inbred strains of mice (CBA, C57 Black and O ₂₀-Amsterdam) or from a partly inbred strain (LE) of piebald rats are used than with the particles isolated from the livers of the former animals, all animals being maintained on the standard laboratory diet. The order of activity of the nucleotides appeared to be: adenosine di- ≥ -tri- ≫ or > -monophosphate, the latter being in many cases scarcely effective, if at all. Evidence has been obtained³ that the adenine nucleotides, added in a sufficiently low concentration as to make any chelating effect unlikely, were especially active when added in conjunction with succinate. The conclusion was, therefore, drawn that the protective effect of the latter compounds on the onset of the thyroxine-induced swelling (that is, the retardation thereof) was mediated by promoting the process of oxidative phosphorylation under the adverse conditions of the deficient medium. This view has now been substantiated by the following results, which may also shed some further light on the anomalous effects of 2 : 4-dinitrophenol (DNP) on the swelling of isolated liver mitochondria.