Cytochalasin A and respiratory inhibition in the water mold Achlya ambisexualis

Cytochalasin A, a potent thiol-blocking fungal metabolite, inhibited respiration of the freshwater fungus Achlya ambisexualis rapidly and irreversibly. Spores, germlings, and mycelia of the fungus were susceptible; the order of susceptibility was mycelia > germlings > spores. Although cytochalasin A inhibited glucose uptake in Achlya germlings. the respiratory inhibition was not due to inhibition of substrate transport. Other cytochalasins tested (cytochalasins B, D, and E) had little or no effect on respiration. Among several other thiol blockers that suppressed respiration in Achlya, only mercuric chloride was more effective than cytochalasin A in inhibiting mycelial respiration. Maleimide derivatives, including N-ethyimaleimide, were one-fifth as effective as cytochalasin A. In isolated Achlya mitochondria, cytochalasin A inhibited oxidation of pyruvate but not of α-ketoglutarate or succinate. Inhibition of pyruvate oxidation was reversible and was not attributable to inhibition of mitochondrial uptake of pyruvate. Thiol blockers effective in the intact system also inhibited respiration of mitochondria. With the exception of reversibility, cytochalasin A inhibition of mitochondria and intact mycelium was similar in the parameters examined.