oligomycins

Summary

Summary: A closely related group of toxic substances elaborated by various strains of Streptomyces. They are 26-membered macrolides with lactone moieties and double bonds and inhibit various ATPases, causing uncoupling of phosphorylation from mitochondrial respiration. Used as tools in cytochemistry. Some specific oligomycins are RUTAMYCIN, peliomycin, and botrycidin (formerly venturicidin X).

Top Publications

  1. Grover G, Marone P, Koetzner L, Seto Young D. Energetic signalling in the control of mitochondrial F1F0 ATP synthase activity in health and disease. Int J Biochem Cell Biol. 2008;40:2698-701 pubmed publisher
    ..Selective hydrolase inhibition seen with the small molecule BMS-199264 suggests a conformational change in the F1F0 ATPase enzyme when switching from synthase to hydrolase activity. ..
  2. Smaili S, Hsu Y, Sanders K, Russell J, Youle R. Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential. Cell Death Differ. 2001;8:909-20 pubmed
    ..Taken together, our results suggest that alterations in mitochondrial energization associated with apoptosis can initiate Bax docking to mitochondria. ..
  3. Kaasik A, Veksler V, Boehm E, Novotova M, Minajeva A, Ventura Clapier R. Energetic crosstalk between organelles: architectural integration of energy production and utilization. Circ Res. 2001;89:153-9 pubmed
    ..Such direct crosstalk between organelles may explain the preserved cardiac function of CK-deficient mice under moderate workloads. ..
  4. Cañas N, Valero T, Villarroya M, Montell E, Vergés J, Garcia A, et al. Chondroitin sulfate protects SH-SY5Y cells from oxidative stress by inducing heme oxygenase-1 via phosphatidylinositol 3-kinase/Akt. J Pharmacol Exp Ther. 2007;323:946-53 pubmed
  5. Affourtit C, Brand M. Uncoupling protein-2 contributes significantly to high mitochondrial proton leak in INS-1E insulinoma cells and attenuates glucose-stimulated insulin secretion. Biochem J. 2008;409:199-204 pubmed
    ..We propose that the high mitochondrial proton leak in beta-cells is a mechanism which amplifies the effect of physiological UCP2 regulators on cytoplasmic ATP/ADP and hence on insulin secretion. ..
  6. Zima A, Pabbidi M, Lipsius S, Blatter L. Effects of mitochondrial uncoupling on Ca(2+) signaling during excitation-contraction coupling in atrial myocytes. Am J Physiol Heart Circ Physiol. 2013;304:H983-93 pubmed publisher
    ..These findings may therefore provide insight into the consequences of mitochondrial uncoupling for ion homeostasis, SR Ca(2+) release, and excitation-contraction coupling in ischemia at the cellular and subcellular level. ..
  7. Ko Y, Delannoy M, Hullihen J, Chiu W, Pedersen P. Mitochondrial ATP synthasome. Cristae-enriched membranes and a multiwell detergent screening assay yield dispersed single complexes containing the ATP synthase and carriers for Pi and ADP/ATP. J Biol Chem. 2003;278:12305-9 pubmed
    ..They also provide evidence that the cristae are a subcompartment of the inner membrane. ..
  8. Homareda H, Ishii T, Takeyasu K. Binding domain of oligomycin on Na(+),K(+)-ATPase. Eur J Pharmacol. 2000;400:177-83 pubmed
    ..Oligomycin depressed the activation by Na(+) of the chimeric Ca(2+)-ATPase activity. These findings suggest that the 200 N-terminal amino acids of the Na(+), K(+)-ATPase alpha-subunit include a binding domain for oligomycin. ..
  9. Brown S, Hosking P, Li J, Williams N. ATP synthase is responsible for maintaining mitochondrial membrane potential in bloodstream form Trypanosoma brucei. Eukaryot Cell. 2006;5:45-53 pubmed
    ..These results support the role of the ATP synthase in the maintenance of the mitochondrial membrane potential in bloodstream form T. brucei. ..

More Information

Publications62

  1. Angelin A, Bonaldo P, Bernardi P. Altered threshold of the mitochondrial permeability transition pore in Ullrich congenital muscular dystrophy. Biochim Biophys Acta. 2008;1777:893-6 pubmed publisher
  2. Karawajew L, Rhein P, Czerwony G, Ludwig W. Stress-induced activation of the p53 tumor suppressor in leukemia cells and normal lymphocytes requires mitochondrial activity and reactive oxygen species. Blood. 2005;105:4767-75 pubmed
  3. Shchepina L, Pletjushkina O, Avetisyan A, Bakeeva L, Fetisova E, Izyumov D, et al. Oligomycin, inhibitor of the F0 part of H+-ATP-synthase, suppresses the TNF-induced apoptosis. Oncogene. 2002;21:8149-57 pubmed
    ..A role of oligomycin-sensitive F0 component of H+-ATP-synthase in the TNF-induced PTP opening and apoptosis is suggested. ..
  4. Vesce S, Jekabsons M, Johnson Cadwell L, Nicholls D. Acute glutathione depletion restricts mitochondrial ATP export in cerebellar granule neurons. J Biol Chem. 2005;280:38720-8 pubmed
    ..The initial bioenergetic consequence of neuronal GSH depletion in this model is thus an inhibition of ATP export, which precedes other forms of mitochondrial dysfunction. ..
  5. Lemeshko V, Kugler W. Synergistic inhibition of mitochondrial respiration by anticancer agent erucylphosphohomocholine and cyclosporin A. J Biol Chem. 2007;282:37303-7 pubmed
    ..Our findings provide new insight into the mechanisms by which these unusual alterations of mitochondria might be involved in anticancer activity of alkylphosphocholines. ..
  6. Mills K, Woodgate L, Gilkes A, Walsh V, Sweeney M, Brown G, et al. Inhibition of mitochondrial function in HL60 cells is associated with an increased apoptosis and expression of CD14. Biochem Biophys Res Commun. 1999;263:294-300 pubmed
    ..These results suggest that inhibition of the components of the mitochondrial pathways may lead to the marking of some cells, via CD14, for cell death, whilst allowing commitment to differentiation to occur in the surviving population. ..
  7. Coort S, Hasselbaink D, Koonen D, Willems J, Coumans W, Chabowski A, et al. Enhanced sarcolemmal FAT/CD36 content and triacylglycerol storage in cardiac myocytes from obese zucker rats. Diabetes. 2004;53:1655-63 pubmed
  8. Aronis A, Melendez J, Golan O, Shilo S, Dicter N, Tirosh O. Potentiation of Fas-mediated apoptosis by attenuated production of mitochondria-derived reactive oxygen species. Cell Death Differ. 2003;10:335-44 pubmed
    ..Similar observations were demonstrated in isolated rat liver mitochondria. These data show that ROS production is important in receptor-mediated apoptosis, playing a pivotal role in cell survival. ..
  9. Irwin W, Bergamin N, Sabatelli P, Reggiani C, Megighian A, Merlini L, et al. Mitochondrial dysfunction and apoptosis in myopathic mice with collagen VI deficiency. Nat Genet. 2003;35:367-71 pubmed
    ..These findings indicate that collagen VI myopathies have an unexpected mitochondrial pathogenesis that could be exploited for therapeutic intervention. ..
  10. Luiken J, Coort S, Willems J, Coumans W, Bonen A, Van der Vusse G, et al. Contraction-induced fatty acid translocase/CD36 translocation in rat cardiac myocytes is mediated through AMP-activated protein kinase signaling. Diabetes. 2003;52:1627-34 pubmed
    ..We conclude that AMP kinase regulates cardiac FA use through mobilization of FAT/CD36 from a contraction-inducible intracellular storage compartment. ..
  11. Hawley S, Gadalla A, Olsen G, Hardie D. The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes. 2002;51:2420-5 pubmed
    ..Our results also show that AMPK can be activated by mechanisms other than changes in the cellular AMP-to-ATP ratio. ..
  12. Singh S, Khar A. Differential gene expression during apoptosis induced by a serum factor: role of mitochondrial F0-F1 ATP synthase complex. Apoptosis. 2005;10:1469-82 pubmed
  13. Ikemoto H, Tani E, Ozaki I, Kitagawa H, Arita N. Calphostin C-mediated translocation and integration of Bax into mitochondria induces cytochrome c release before mitochondrial dysfunction. Cell Death Differ. 2000;7:511-20 pubmed
  14. Tinel H, Cancela J, Mogami H, Gerasimenko J, Gerasimenko O, Tepikin A, et al. Active mitochondria surrounding the pancreatic acinar granule region prevent spreading of inositol trisphosphate-evoked local cytosolic Ca(2+) signals. EMBO J. 1999;18:4999-5008 pubmed
    ..When mitochondrial function is inhibited, this barrier disappears and the Ca(2+) signals spread all over the cytosol. ..
  15. McKenzie M, Liolitsa D, Akinshina N, Campanella M, Sisodiya S, Hargreaves I, et al. Mitochondrial ND5 gene variation associated with encephalomyopathy and mitochondrial ATP consumption. J Biol Chem. 2007;282:36845-52 pubmed
    ..These data suggest that in response to impaired respiration due to the mtDNA mutation, mitochondria consume ATP to maintain Deltapsim, representing a potential pathophysiological mechanism in human mitochondrial disease. ..
  16. Zullo S, Parks W, Chloupkova M, Wei B, Weiner H, Fenton W, et al. Stable transformation of CHO Cells and human NARP cybrids confers oligomycin resistance (oli(r)) following transfer of a mitochondrial DNA-encoded oli(r) ATPase6 gene to the nuclear genome: a model system for mtDNA gene therapy. Rejuvenation Res. 2005;8:18-28 pubmed
    ..Preliminary experiments on human cybrids homoplasmic for the NARP mutation (kindly supplied by D.C. Wallace), transformed with our construct, display an increased oligomycin resistance that supports these suppositions. ..
  17. Pucci B, Bertani F, Karpinich N, Indelicato M, Russo M, Farber J, et al. Detailing the role of Bax translocation, cytochrome c release, and perinuclear clustering of the mitochondria in the killing of HeLa cells by TNF. J Cell Physiol. 2008;217:442-9 pubmed publisher
    ..The release of cytochrome c depends on the induction of the mitochondrial permeability transition but not ATP content. ..
  18. Starkov A, Fiskum G, Chinopoulos C, Lorenzo B, Browne S, Patel M, et al. Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species. J Neurosci. 2004;24:7779-88 pubmed
    ..The data strongly indicate that KGDHC is a primary site of ROS production in normally functioning mitochondria. ..
  19. Talbot J, David G, Barrett E. Inhibition of mitochondrial Ca2+ uptake affects phasic release from motor terminals differently depending on external [Ca2+]. J Neurophysiol. 2003;90:491-502 pubmed
    ..5 mM Ca2+. A similar convergence was measured in oligomycin, which inhibits mitochondrial ATP synthesis without depolarizing mitochondria, but quantal contents fell to <20 when mitochondria were depolarized in 2 mM Ca2+. ..
  20. Wojtczak L, Nikitina E, Czyz A, Skulskii I. Cuprous ions activate glibenclamide-sensitive potassium channel in liver mitochondria. Biochem Biophys Res Commun. 1996;223:468-73 pubmed
  21. Hallstrom T, Moye Rowley W. Divergent transcriptional control of multidrug resistance genes in Saccharomyces cerevisiae. J Biol Chem. 1998;273:2098-104 pubmed
    ..This suggests the possibility that UASYOR1 has promoter-specific sequence requirements that are satisfied by another Pdr1p/Pdr3p-regulated gene but not by a heterologous promoter. ..
  22. Carrasco A, Dzeja P, Alekseev A, Pucar D, Zingman L, Abraham M, et al. Adenylate kinase phosphotransfer communicates cellular energetic signals to ATP-sensitive potassium channels. Proc Natl Acad Sci U S A. 2001;98:7623-8 pubmed
    ..Assigning a signal processing role to adenylate kinase identifies a phosphorelay mechanism essential for efficient coupling of cellular energetics with K(ATP) channels and associated functions. ..
  23. Gizatullina Z, Grapengiesser E, Shabalina I, Nedergaard J, Heldin C, Aspenstrom P. Effect of transforming growth factor-beta on calcium homeostasis in prostate carcinoma cells. Biochem Biophys Res Commun. 2003;304:643-9 pubmed
    ..The results implicate that TGF-beta1 affects the function of the mitochondria and may be of significance for the understanding of the proapoptotic effect of TGF-beta1 in these cells. ..
  24. Cheranov S, Jaggar J. Mitochondrial modulation of Ca2+ sparks and transient KCa currents in smooth muscle cells of rat cerebral arteries. J Physiol. 2004;556:755-71 pubmed
    ..Data also suggest that mitochondrial depolarization inhibits Ca(2+) sparks and transient K(Ca) currents via PTP opening and a decrease in intramitochondrial [Ca(2+)]. ..
  25. Johnson K, Cleary J, Fierke C, Opipari A, Glick G. Mechanistic basis for therapeutic targeting of the mitochondrial F1F0-ATPase. ACS Chem Biol. 2006;1:304-8 pubmed
    ..They also represent key criteria for the development of therapeutic F 1 F o -ATPase inhibitors, which should have utility across a range of areas. ..
  26. Habets D, Coumans W, El Hasnaoui M, Zarrinpashneh E, Bertrand L, Viollet B, et al. Crucial role for LKB1 to AMPKalpha2 axis in the regulation of CD36-mediated long-chain fatty acid uptake into cardiomyocytes. Biochim Biophys Acta. 2009;1791:212-9 pubmed publisher
    ..In addition, an unknown dipyridamole-activated pathway can stimulate cardiac LCFA utilization by activating signaling components downstream of AMPK. ..
  27. Knopp A, Thierfelder S, Doepner B, Benndorf K. Mitochondria are the main ATP source for a cytosolic pool controlling the activity of ATP-sensitive K(+) channels in mouse cardiac myocytes. Cardiovasc Res. 2001;52:236-45 pubmed
    ..The activity of K(ATP) channels in cardiomyocytes of mice is controlled by a cytosolic [ATP] pool for which oxidative phosphorylation is the predominant ATP source. ..
  28. Lysenkova L, Turchin K, Danilenko V, Korolev A, Preobrazhenskaya M. The first examples of chemical modification of oligomycin A. J Antibiot (Tokyo). 2010;63:17-22 pubmed publisher
    ..The structures of the compounds obtained were supported by NMR and mass spectrometry methods including the (15)N-labeling of compounds. ..
  29. Grover G, Malm J. Pharmacological profile of the selective mitochondrial F1F0 ATP hydrolase inhibitor BMS-199264 in myocardial ischemia. Cardiovasc Ther. 2008;26:287-96 pubmed publisher
    ..These data also suggest that the reversal of the synthase and hydrolase activities is not merely a chemical reaction run in reverse. ..
  30. Reis Y, Bernardo Faura M, Richter D, Wolf T, Brors B, Hamacher Brady A, et al. Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis. PLoS ONE. 2012;7:e28694 pubmed publisher
    ..We further discuss the benefits of a flexible systematic approach for elucidating specific and general relationships between mitochondrial morphology and apoptosis. ..
  31. Hashimi H, Benkovicová V, Cermáková P, Lai D, Horváth A, Lukes J. The assembly of F(1)F(O)-ATP synthase is disrupted upon interference of RNA editing in Trypanosoma brucei. Int J Parasitol. 2010;40:45-54 pubmed publisher
    ..In addition, the F(1) moiety of complex V appears to exist as a dimer in steady state conditions and contains the ATP4 subunit traditionally assigned to the F(O) sub-complex. ..
  32. Abarca Rojano E, Muñiz Hernández S, Moreno Altamirano M, Mondragón Flores R, Enríquez Rincón F, Sánchez García F. Re-organization of mitochondria at the NK cell immune synapse. Immunol Lett. 2009;122:18-25 pubmed publisher
  33. Nilsen J, Diaz Brinton R. Mechanism of estrogen-mediated neuroprotection: regulation of mitochondrial calcium and Bcl-2 expression. Proc Natl Acad Sci U S A. 2003;100:2842-7 pubmed
  34. Korystov Y, Kublik L, Kudryavtsev A, Levitman M, Shaposhnikova V, Drinyaev V, et al. Opposite effects of low oligomycin concentrations on the apoptosis of normal and tumor cells. Dokl Biol Sci. 2003;392:475-7 pubmed
  35. Allen A, Graham A. Mitochondrial function is involved in regulation of cholesterol efflux to apolipoprotein (apo)A-I from murine RAW 264.7 macrophages. Lipids Health Dis. 2012;11:169 pubmed publisher
    ..Bioavailable antioxidants, targeted to mitochondria and capable of sustaining effective mitochondrial function, may therefore prove effective in maintenance of arterial health. ..
  36. Dikov D, Bereiter Hahn J. Inner membrane dynamics in mitochondria. J Struct Biol. 2013;183:455-466 pubmed publisher
    ..Thus position of cristae seems to be rather stable, but they regularly disassemble close to fission sites. Treatment with oligomycin strongly reduces "wobbling" activity. ..
  37. García Parra P, Maroto M, Cavaliere F, Naldaiz Gastesi N, Alava J, Garcia A, et al. A neural extracellular matrix-based method for in vitro hippocampal neuron culture and dopaminergic differentiation of neural stem cells. BMC Neurosci. 2013;14:48 pubmed publisher
    ..In addition, neural ECM-coated substrates increased neuronal survival and neuronal differentiation efficiency as compared to cationic polymers such as poly-L-lysine. ..
  38. Kashemsant N, Chan C. Impact of uncoupling protein-2 overexpression on proinsulin processing. J Mol Endocrinol. 2006;37:517-26 pubmed
  39. Guigas B, Bertrand L, Taleux N, Foretz M, Wiernsperger N, Vertommen D, et al. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on glucokinase translocation. Diabetes. 2006;55:865-74 pubmed
  40. Malka F, Guillery O, Cifuentes Diaz C, Guillou E, Belenguer P, Lombes A, et al. Separate fusion of outer and inner mitochondrial membranes. EMBO Rep. 2005;6:853-9 pubmed
    ..The separate fusion of outer and inner membranes and the different requirements of these fusion reactions point to the existence of fusion machineries that can function separately. ..
  41. Rydberg E, Salomonsson L, Hulten L, Norén K, Bondjers G, Wiklund O, et al. Hypoxia increases 25-hydroxycholesterol-induced interleukin-8 protein secretion in human macrophages. Atherosclerosis. 2003;170:245-52 pubmed
    ..Thus, hypoxia in atherosclerotic plaques may increase the secretion of IL-8 from oxysterol-containing foam cells, which subsequently may accelerate the progression of atherosclerosis. ..
  42. Paxinou E, Weisse M, Chen Q, Souza J, Hertkorn C, Selak M, et al. Dynamic regulation of metabolism and respiration by endogenously produced nitric oxide protects against oxidative stress. Proc Natl Acad Sci U S A. 2001;98:11575-80 pubmed
  43. Chernyak B, Bernardi P. The mitochondrial permeability transition pore is modulated by oxidative agents through both pyridine nucleotides and glutathione at two separate sites. Eur J Biochem. 1996;238:623-30 pubmed
  44. Boyer P, Cross R, Momsen W. A new concept for energy coupling in oxidative phosphorylation based on a molecular explanation of the oxygen exchange reactions. Proc Natl Acad Sci U S A. 1973;70:2837-9 pubmed
    ..This release could logically involve energy-requiring protein conformational change. ..
  45. Comelli M, Di Pancrazio F, Mavelli I. Apoptosis is induced by decline of mitochondrial ATP synthesis in erythroleukemia cells. Free Radic Biol Med. 2003;34:1190-9 pubmed
  46. Billups B, Forsythe I. Presynaptic mitochondrial calcium sequestration influences transmission at mammalian central synapses. J Neurosci. 2002;22:5840-7 pubmed
    ..Without detectable thapsigargin-sensitive presynaptic calcium stores, we conclude that mitochondria are the major organelle regulating presynaptic calcium at central glutamatergic terminals. ..
  47. Rego A, Vesce S, Nicholls D. The mechanism of mitochondrial membrane potential retention following release of cytochrome c in apoptotic GT1-7 neural cells. Cell Death Differ. 2001;8:995-1003 pubmed
    ..These results indicate that the maintenance of Delta Psi(M) following release of cyt c may be a consequence of ATP synthase reversal and cytoplasmic ATP hydrolysis in STS-treated GT1-7 cells. ..
  48. Oropesa M, de la Mata M, Maraver J, Cordero M, Cotán D, Rodriguez Hernandez A, et al. Apoptotic microtubule network organization and maintenance depend on high cellular ATP levels and energized mitochondria. Apoptosis. 2011;16:404-24 pubmed publisher
    ..These data provide new explanations for the role of AMN and mitochondria during apoptosis. ..
  49. Calupca M, Prior C, Merriam L, Hendricks G, Parsons R. Presynaptic function is altered in snake K+-depolarized motor nerve terminals containing compromised mitochondria. J Physiol. 2001;532:217-27 pubmed
    ..Therefore, the proposed sustained elevation of [Ca2+]i could occur more rapidly. ..
  50. Reilly J, Maher P. Importin beta-mediated nuclear import of fibroblast growth factor receptor: role in cell proliferation. J Cell Biol. 2001;152:1307-12 pubmed
    ..These data are the first description of a nuclear import pathway for transmembrane growth factor receptors and elucidate a novel signal transduction pathway from the cell surface to the nucleus. ..
  51. Walker J, Gay N, Powell S, Kostina M, Dyer M. ATP synthase from bovine mitochondria: sequences of imported precursors of oligomycin sensitivity conferral protein, factor 6, and adenosinetriphosphatase inhibitor protein. Biochemistry. 1987;26:8613-9 pubmed
    ..These experiments indicate that the bovine and human inhibitor and bovine F6 proteins are encoded by single genes but suggest the possibility of the presence in both species of more than one gene (or pseudogenes) for the OSCP. ..
  52. McArdle J, Sellin L, Coakley K, Potian J, Hognason K. Mefloquine selectively increases asynchronous acetylcholine release from motor nerve terminals. Neuropharmacology. 2006;50:345-53 pubmed
    ..This elevation of Ca2+ concentration selectively increases asynchronous transmitter release since 10 microM mefloquine did not alter stimulus-evoked transmsitter release. ..
  53. Granger D, Marsolais M, Burry J, Laprade R. V-type H+-ATPase in the human eccrine sweat duct: immunolocalization and functional demonstration. Am J Physiol Cell Physiol. 2002;282:C1454-60 pubmed
    ..These results strongly suggest that a V-ATPase is involved in proton secretion in the human eccrine SD. ..