F-ATPase exists in the bacterial plasma membrane, mitochondrial inner membrane, and chloroplast thylakoid membrane. Specifically, it uses proton gradients to drive ATP synthesis. It releases newly formed ATP from the active site of the F-ATPase. Besides, it allowing protons to passively pass through the membrane along its electrochemical gradient and using the energy released by the transport reaction. When hypoxia destroys the mitochondrial electrochemical gradient, F0F1 ATP synthase switches from ATP synthesis to ATP hydrolysis. Therefore, it is the main consumer of ATP during severe ischemia. Moreover, Mitochondrial proton F0F1 ATPase/ATP synthase synthesizes ATP during oxidative phosphorylation. The enzyme can be divided into two main complexes: F1 and F0. Furthermore, F1 is a water-soluble catalytic complex. F0 consists of several membrane proteins and oligomycin sensitivity conferring protein (OSCP).

Meanwhile, the four complexes of the respiratory chain undergo a series of redox reactions. Nonetheless, it results in the reduction of oxygen to water. They can maintain the proton pumping activity of complexes I, III and IV. The latter produces an electrochemical gradient called proton dynamics on IMM, which is absolutely necessary for F-ATP synthase to produce ATP. Particularly, the Cell surface F-ATPase subunit is the key in tumor growth and inhibition. Importantly, it may be a potential therapeutic target for cancer. Today, we will introduce a mitochondrial F0F1-ATPase inhibitor, Oligomycin A.

Oligomycin A (MCH 32) Acts as a Mitochondrial F0F1-ATPase Inhibitor.

First of all, Oligomycin A (MCH 32), created by Streptomyces, is a mitochondrial F0F1-ATPase inhibitor with a Ki of 1 μM. Particularly, Oligomycin A shows anti-fungal activity.

In the second place, Oligomycin A shows cytotoxic to the NCI-60 cell lines, with a GI50 of 10 nM. Obviously, Oligomycin A also inhibits the activity of Triton X-100-solubilized ATPase with a Ki of 0.1 μM. Furthermore, Oligomycin A inhibits the ability of spermatozoa to achieve feasible in vitro capacitation (IVC). Additionally, Oligomycin A also suppresses progesterone-induced in vitro acrosome exocytosis (IVAE) as well as the concomitant peaks of O2 consumption and ATP levels.

All in all, Oligomycin A (MCH 32) is a mitochondrial F0F1-ATPase inhibitor.


Ramió-Lluch L, et al. Reprod Fertil Dev. 2014;26(6):883-97.