Effect of methyl mercury on phosphorylation, transport, and oxidation in mammalian mitochondria.
the toxic effects of CH3HgCL on mitochondria of  mammalian organs including human and rat liver were examined. [203Hg]CH3HGCl was bound mainly to mitochondrial proteins. The binding was not effected by the energy state of mitochondria. The state 3  respiration, oxidative phosphorylation and 32Pi-ATP exchange reaction were inhibited by 10 to 50 nmol of CH3HgCl per mg of mitochondrial protein, while NADH-and succinate-dehydrogenase and ATPase were more resistant to it The difference spectrum of the treated mitochondria indicated that the point of inhibition was located after flavin and before cytochrome b. Mitochondrial swelling was induced by CH3HgCl, in accordance with previous morphological observations  in vivo. The swelling, stimulation of ATPase and energy-dependent H+ extrusion cauded by CH3HgCl were equally dependent on K+. Under these conditions, uptake of K+ by mitochondria was increased and the membrane potential was dissipated. Unlike the case with other organomercuric compounds, transport of phosphate was not inhibited by CH3HgCl. When tested on liposomes, CH3HgCl itself was not lipid-soluble, as some organomercuric compounds are, and was not an uncoupler or a K+-carrier. It was concluded that protein bound CH3HgS-induced K+ uptake into mitochondria and the resulting loss of membrane potential was the major cause of uncoupling, though at higher concentrations, the electron transport system was also inhibited.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004579:Electron Transport / Q000187:drug effects; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008767:Methylmercury Compounds / Q000378:metabolism / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D011522:Protons; D051381:Rats
D008767:Methylmercury Compounds; D011522:Protons; D000251:Adenosine Triphosphatases; D011188:Potassium