Abstract
Abstract 1. 1. The antibiotic Dio-9 inhibits the acceptor-controlled respiration of intact rat-liver mitochondria in a phosphate-containing medium. Essentially the same effects have been found with glutamate, β-hydroxybutyrate, α-ketoglutarate, succinate and the ascorbate-tetramethyl-p-phenylenediamine system as substrate. 2. 2. Inhibition of respiration by Dio-9 in a phosphate-containing system cannot be reversed by 2,4-dinitrophenol. However, if 2,4-dinitrophenol is added in uncoupling concentrations (0.1 mM) prior to the antibiotic there is no inhibition of respiration by Dio-9. 3. 3. The inhibition of respiration by Dio-9 is preceded by a short burst of increased oxygen uptake. 4. 4. The inhibition of respiration by Dio-9 is dependent upon the presence of inorganic phosphate or arsenate in the incubation medium. In the absence of phosphate, Dio-9 only stimulates the respiration which is further accelerated by dinitrophenol. 5. 5. Dio-9 stimulates respiration in the presence of oligomycin or 2-n-heptyl-4-hydroxyquinolineN-oxide in the absence of phosphate but not in its presence. 6. 6. Arsenate-stimulated respiration is only slightly inhibited by Dio-9. However, the increased respiration produced by 2,4-dinitrophenol in the presence of arsenate is not obtained in the presence of Dio-9. 7. 7. Dio-9 has a much smaller effect on sonicated mitochondria or on the Keilin and Hartree heart-muscle preparation. 8. 8. Dio-9 causes a minor swelling of rat-liver mitochondria which is potentiated by inorganic phosphate. 9. 9. The antibiotic has little effect on the 2,4-dinitrophenol-induced ATPase of freshly prepared mitochondria although it inhibits the ATPase of aged mitochondria. 10. 10. The possible mode of action of Dio-9 is discussed.
Published Version
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