Inhibition of mitochondrial respiration and uncoupling of oxidative phosphorylation by fractions of the Shigella paradysenteriae type III-somatic antigen

Abstract

Somatic antigen preparations derived from S. paradysenteriae type III were found to inhibit oxygen consumption in rat or mouse liver mitochondria. The inhibitory effect was traced to a naturally occurring (native) haptenic polysaccharide contaminating these preparations. Under the standard test conditions, the hapten inhibited preferentially the oxidation of substrates the dehydrogenases of which are linked to pyridine nucleotides; the succinic oxidase showed a much lower degree of inhibition. The antigenic lipo-polysaccharide-protein complex (“complete somatic antigen”) in a highly purified state did not affect mitochondrial respiration, while polysaccharidic haptens obtained by chemical degradation of the antigenic complex exhibited the inhibition pattern characteristic for the native hapten. Both the native hapten and its artificial congeners uncoupled oxidative phosphorylation in rat liver mitochondria. The mechanism of the inhibitory action in vitro and its relation to toxicity in vivo are discussed.