Question

When the antibiotic valinomycin is added to actively respiring mitochondria, several things happen: the yield of ATP decreases, the rate of O2 consumption increases, heat is released, and the pH gradient across the inner mitochondrial membrane increases. Does valinomycin act as an uncoupler or as an inhibitor of oxidative phosphorylation? Explain the experimental observations in terms of the antibiotic’s ability to transfer K+ ions across the inner mitochondrial membrane.

Answer 1

Valinomycin produces higher steady state potassium phosphate swelling which can be reversed to give active shrinkage if mersalyl is added to block the Pi−/OH− antiporter. Respiration declines concurrently. Uncouplers accelerate the shrinkage and restore the respiration.