Oligomycin

Mitochondrial ATP Synthase Inhibitor. Oligomycin is a natural antibiotic isolated from Streptomyces diastatochromogenes which inhibits mitochondrial H\\^+\\-ATP synthase. It is primarily found to act as an inhibitor of mitochondrial respiration and swelling. This antibiotic is widely used as an inhibitor of oxidative phosphorylation.

Oligomycin inhibits the H\\^+\\- ATP-synthase by binding to the Oligomycin sensitivity-conferring protein (OSCP) at the F(o) subunits 6 and 9 which are found in the stalk of the F1F0-ATPase complex. This binding blocks the proton conductance and inhibits the synthesis of mitochondrial ATP. Because of its activity, it can also be used to reduce the number of parameters (such as ER Ca²⁺ release, exocytotoxicity and apopotosis) which are affected by mitochondrial depolarization.

Oligomycin at high concentrations may also inhibit the plasma membrane Na\\^+\\-K\\^+\\-ATPase. Interaction of Oligomycin with the Na\\^+\\ occlusion site on the extracellular side of Na/K-ATPase, delays Na\\^+\\ release to the extracellular side without inducing a conformational change. Although Oligomycin stimulated Na\\^+\\ binding to Na\\^+\\/K\\^+\\-ATPase, it inhibited Na\\^+\\/Na\\^+\\ exchange, and did not affect either Na\\^+\\-dependent AD/-ATP exchange or K\\^+\\-dependent phosphatase activity.

These inhibitory properties have been attributed to its ability to occlude the transition of E1~P (high energy intermediate) to E2-P (low energy intermediate) by oligomycin binding to E1~P. Cell Signaling Activators and Inhibitors; Mitochondrial ATPase Inhibitor.

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