Interaction of the aminoglycoside antibiotic dihydrostreptomycin with the H+-ATPase of mitochondria.

ABSTRACT

In this paper a study is presented of the effect of dihydrostreptomycin on the H+-ATPase of the inner mitochondrial membrane. The antibiotic caused at concentrations of 1-5 X 10(-3)M a marked enhancement of the hydrolytic activity of the H+-ATPase complex in intact mitochondria and submitochondrial particles which was accompanied, in the latter, by enhancement of passive transmembrane proton conduction by the complex. The stimulation by dihydrostreptomycin of ATP hydrolysis resulted in a suppression of the sensitivity of this activity to inhibition by oligomycin. On the other hand the dihydrostreptomycin-promoted proton conduction in submitochondrial particles was suppressed by oligomycin. At concentrations above 10(-2)M dihydrostreptomycin caused inhibition of the activity of both membrane bound and isolated H+-ATPase. In submitochondrial particles devoid of the catalytic moiety (F1) of the H+-ATPase complex, dihydrostreptomycin caused partial inhibition of proton conductivity. It is concluded that the antibiotic uncouples the hydrolytic activity of the catalytic moiety (F1) from transmembrane proton conduction by the membrane sector (F0) of the ATPase complex. This effect can be followed at higher concentrations of dihydrostreptomycin by inhibition of the catalytic activity of F1 and, when F1 is removed from the membrane, by inhibition of transmembrane proton conduction by F0.