Oligomycin is a macrolide antibiotic complex from Streptomyces. It is an inhibitor of mitochondrial ATP synthase as first reported in 1958 by Henry Lardy et al. Oligomycins exhibit apoptotic cytotoxicity and mitochondrial toxicity.
The Oligomycin complex was first reported in 1954, from a strain of Streptomyces diastatochromogenes from soil and was highly active against fungi. The Oligomycin class includes the analogs/isomers A through G. Different isomers are highly specific for the disruption of mitochondrial metabolism. The Oligomycins have antifungal, antibacterial and antitumor properties.
Oligomycin is freely soluble in ethanol. It is soluble in DMSO. It is practically insoluble in water.
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.|
|Mechanism of Action||Oligomycin inhibits phosphoryl group transfer in membrane-bound ATP synthase. The result is that mitochondrial ATP is not synthesized. It inhibits F0F1-ATPase, blocks proton translocation leading to hyperpolarization of inner mitochondrial membrane.
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 (Symersky et al, 2012). The residues involved in the binding site are conserved from yeast to humans.
|Spectrum||Active against fungi including Aspergillus, Penicillium.|
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 1uM for MEF’s and 2uM 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||Freely soluble in ethanol. Soluble in DMSO. Practically insoluble in water.|
Atzmon A et al (2018) Drug screening identifies sigma-1-receptor as a target for the therapy of VWM leukodystrophy. Front. Mol. Neurosci 11. 336 pp. doi 10.3389
Fitch ME, Chang C and Parslow TG (2000). The BH3 domain is required for caspase-independent cell death induced by Bax and Oligomycin. Cell Death and Differen. 7(4):338-349
Furth N et al (2018) LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state. Life Sci. Alliance. 1(5):e201800171 PMID 30456386
Jastroch M (2010) Mitochondrial proton and electron leaks. Essays in Biochem. 47:53-67 doi:10.1042/bse0470053
Li YC et al (2002) Mitochondria-targeting drug Oligomycin blocked P-glycoprotein activity and triggered apoptosis in doxorubicin-resistant HepG2 cells. Pharmacol. 50:55-62
Raini G et al (2017) Mutant elF2B leads to impaired mitochondrial oxidative phosphorylation in vanishing white matter disease. J. Neurochem. 141(5):694-707
Smith RM, Peterson WH and McCoy E (1954) Oligomycin, a new antifungal antibiotic. Antibiot. Chemother. 4(9):962-970
Symersky J et al (2012) Oligomycin frames a common drug-binding site in the ATP synthase. Proc. Natl. Acad. Sci. USA 109(35):13961-13965