Oligomycin A is a dominant analog of the Oligomycin class of macrocyclic lactones isolated from selected strains of Streptomyces sp. The class includes the analogs/isomers A through G. Different isomers are highly specific for the disruption of mitochondrial metabolism. Oligomycin A exhibits a broad biological profile including antifungal, antitumor and nematocidal activities.
Oligomycin A is an inhibitor of mitochondrial F1F0 ATP synthase as first reported in 1958 by Henry Lardy et al. The Oligomycin complex was first reported in 1954, from a strain of Streptomyces diastatochromogenes from soil which was highly active against fungi. Oligomycins exhibit apoptotic cytotoxicity and mitochondrial toxicity.
Oligomycin A is soluble in ethanol, methanol, DMSO and DMF. It has poor water solubility.
Additional Oligomycin products can be found here.
|Application||Oligomycin can be used to demonstrate ‘proton leak’, the depletion of Δp in the presence of the ATP synthase inhibitor. Useful tool in cytochemistry. Used to study effects of ATP depletion.|
Oligomycin A is active against fungi including Aspergillus and Penicillium.
|Mechanism of Action||
Oligomycin inhibits phosphoryl group transfer in mitochondrial membrane-bound ATP synthase (F1F0 ATPase), blocking proton translocation and leading to hyperpolarization of inner mitochondrial membrane. The result is that mitochondrial ATP is not synthesized.
After more than 50 years of studies on the binding site of Oligomycin, a team at the Rosalind Franklin University (North Chicago, IL) discovered that it binds to the subunit-c of the F0 portion of the ATP synthase. The residues involved in the binding site are conserved from yeast to humans (Symersky et al, 2012).
A number of mutations in yeast have been shown to confer resistance to Oligomycin.
|Eukaryotic Cell Culture Applications||
Oligomycin is used to study ATP-linked respiration and for the maximal capacity respiration assay in astrocytes, at 1 µM for MEF’s and 2 µM for astrocytes. It can be used to measure oxygen consumption in commercial kits such as the Mito Stress Test Kit (Agilent). The compound is serially injected to measure ATP-linked respiration. The test can help quantify parameters of mitochondrial respiration and identify mitochondrial dysfunction (Atzmon et al, 2018).
Mitochondria are regulators in apotosis, thus are a target for cancer research. Oligomycin was found to bypass doxorubicin resistance and block P-glycoprotein activity. P-glycoprotein causes multidrug resistance, and extrudes anticancer drugs to the extracellular environment using ATP. The result was that it triggered apoptosis in drug-resistant HepG2 cells (Li et al, 2002).
Oligomycin has been used to study the mechanistic aspects of ATP formation in tumor cell biology and apoptosis.
|Solubility||Oligomycin A is soluble in ethanol, methanol, DMSO and DMF. It has poor water solubility.|
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