Influence of the energetic state of mitochondria on the inhibition of oxidative phosphorylation by N-ethylmaleimide.
N-Ethylmaleimide inhibitory effect on oxidative phosphorylation, adenylic nucleotide translocation, succinate dehydrogenase and succinoxidase activities was studied as a function of the energetic state of mitochondria. 1. Using a reversible thiol reagent (mersalyl), in order to protect the phosphate carrier against irreversible action of N-ethylmaleimide, it was found that: (a) when mersalyl-pretreated mitochondria were in a 'non-energized' state, i.e. preincubated without a substrate and in the presence of rotenone, only a slight inhibition of succinate oxidation coupled to ATP synthesis by N-ethylmaleimide was observed. (b) when mersalyl-pretreated mitochondria were in an 'energized' state, i.e. preincubated in the presence of an oxidizable substrate, N-ethylmaleimide strongly inhibited the coupled oxidation of succinate. 2. Mitochondrial energization was also shown to enhavce the inhibitory effect of N-ethylmaleimide on adenylic nucleotide translocation and succinoxidase activity. However, other sulphydrul groups seem to be involved in the inhibition mechanism, but their function is unknown. 3. As N-ethylmaleimide inhibitory effect increased, an enhancement of N-[14C]ethylmaleimide binding to mitochondrial sulphydryl groups was obtained.
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D004734:Energy Metabolism; D005033:Ethylmaleimide / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D013386:Succinates / Q000378:metabolism
D013386:Succinates; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D005033:Ethylmaleimide