SKU: O037  / 
    CAS Number: 1404-19-9

    Oligomycin

    $145.04 - $966.90

    Oligomycin is a macrolide antibiotic complex from Streptomyces.  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 via inhibition of mitochondrial ATP synthase.  The Oligomycins have antifungal, antibacterial and antitumor properties.  Oligomycin can be used in cytochemistry to study the effects of ATP depletion, specifically to demonstrate ‘proton leak’, the depletion of Δp in the presence of the ATP synthase inhibitor. 

    Oligomycin is freely soluble in ethanol, soluble in DMSO, and practically insoluble in water.

    We also offer:

    • Oligomycin A (O013)
    • Oligomycin B (O018)
    • Oligomycin C (O019)
    • Oligomycin D (O020)
    • Oligomycin E (O021)
    • 21-Hydroxyoligomycin A (H032)
    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, preventing synthesis of mitochondrial ATP.  It inhibits F0F1-ATPase and blocks proton translocation leading to hyperpolarization of the 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.
    Microbiology Applications 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).

    Oligomycin can be used to measure oxygen consumption rate and extracellular acidification rates in breast cancer cell lines, contributing to our understanding of molecular pathways that contribute to breast cancer progression (Furth et al, 2018).
    Cancer Applications 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.

    References

    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