SUMMARY: At an external pH of 3.5, nigericin (which catalyses an electroneutral H/K exchange) abolished the transmembrane proton gradient (ΔpH) of causing a rapid acidification of the cytoplasm from approximately pH 6.0 to pH 3.5. A pronounced loss of viability and fine-structural changes rapidly followed treatment with nigericin. A marked decline in respiration and an even more rapid decrease in cytoplasmic ATP were observed. Activity of at least one cytoplasmic enzyme decreased more slowly. There was no generalized loss in the integrity of the cytoplasmic membrane, as assayed by permeability to inulin or Na or by release of ultraviolet light-absorbing compounds. The loss of viability upon treatment with carbonyl cyanide -chlorophenylhydrazone was similar to that observed with nigericin, so proton influx alone, rather than together with K efflux, was probably involved in the death of the organism. Moreover, acidification of the cytoplasm rather than abolition of the ΔpH was the lethal event, since no loss of viability was observed when the ΔpH was abolished by elevation of the external pH.


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