Interaction of methylmercury chloride with cellular energetics and related processes.

Upon exposure to methylmercury chloride, the whole-cell oxygen uptake by the yeast Saccharomyces cerevisiae ceases. On a fermentable carbon source, carbon dioxide continues to be evolved after respiration has stopped, indicating that fermentation is still active. Dextrose and glycerol uptake also persists until the respective processes, fermentation and respiration, are totally inhibited. Protein and nucleic acid synthesis are blocked with similar concentrations of methylmercury, while cytochrome c, the terminal component of the electron transport chain, is unaltered by the toxicant. Surprisingly, the intracellular ATP is higher in the treated cells than in the controls, although they eventually fall in response to higher concentrations of methylmercury, while cytochrome c, the terminal component of the electron transport chain, is unaltered by the toxicant. Surprisingly, the intracellular ATP is higher in the treated cells than in the controls, although they eventually fall in response to higher concentration or longer exposure. High-pressure liquid chromatography profiles show that the amounts of the other nucleotides are either unaltered or increased. The entire inhibitory process is reversible with time or fresh medium at low methylmercury concentrations. These results do not support the hypothesis expressed by several authors of an inhibition of ATP biosynthesis resulting from membrane perturbation. These data suggest that the decrease in ATP--when induced by the organomercurial--is a secondary process and is not the result of direct mitochondrial toxicity.