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Cell Biology International Feb 2008Oligomycin A, an inhibitor of mitochondrial ATP synthase, provokes simultaneous and different responses in IPLB-LdFB insect cell line. The oligomycin A treatment causes...
Oligomycin A, an inhibitor of mitochondrial ATP synthase, provokes simultaneous and different responses in IPLB-LdFB insect cell line. The oligomycin A treatment causes mitochondrial loss, increase in reactive oxygen species (ROS), destabilization/reorganization of the actin microfilaments and, finally, autophagic cell death. We speculate that oligomycin A affects the mitochondria and that the impairment of these organelles leads to the generation of ROS in quantities that exceed the antioxidant capacity of the cell. This in turn would lead to a feedback loop of increased mitochondrial impairment, amplification of ROS production and the removal of damaged organelles through autophagy.
Topics: Actins; Animals; Cell Line; Mitochondria; Moths; Oligomycins; Reactive Oxygen Species
PubMed: 18093849
DOI: 10.1016/j.cellbi.2007.10.011 -
Agents and Actions Dec 1984Intraperitoneal injection of oligomycin into the rat (0.5 mg per kg, corresponding to the LD33 dose) reduces the oxygen consumption by about 50%, whereas the arterial...
Intraperitoneal injection of oligomycin into the rat (0.5 mg per kg, corresponding to the LD33 dose) reduces the oxygen consumption by about 50%, whereas the arterial pO2 remains normal. The large extent of this decrease points to an involvement of liver and muscle tissue. Triiodothyronine pretreatment (3 doses of 0.075 mg/100 g body weight) is not able to prevent this effect. From the blood metabolites measured glucose, pyruvate and the parameters of lipid metabolism remain unchanged; only lactate is significantly increased, causing compensated metabolic acidosis. Heart rate, systolic blood pressure and electrocardiogram are essentially unchanged. Oliguria, reduced renal excretion of urea and increase of plasma urea also indicate a nephrotoxic action. The results are discussed in comparison with some effects of experimental uremia.
Topics: Animals; Hemodynamics; Kidney; Mitochondria; Oligomycins; Oxygen Consumption; Rats; Rats, Inbred Strains
PubMed: 6532186
DOI: 10.1007/BF01966788 -
Somatic Cell Genetics Nov 1981The inheritance of oligomycin resistance was studied in three mouse L-cell mutants, OLI 2, OLI 4, and OLI 14. All three mutants had previously been shown to have...
The inheritance of oligomycin resistance was studied in three mouse L-cell mutants, OLI 2, OLI 4, and OLI 14. All three mutants had previously been shown to have oligomycin-resistant mitochondrial ATPase activity. In addition, OLI 14 has DCCD-resistant mitochondrial ATPase activity and an altered DCCD-binding protein. Oligomycin-resistant cells were enucleated and fused with oligomycin-sensitive cells under a variety of selective regimes designed to allow growth of oligomycin-resistant cybrids. No transfer of oligomycin resistance via the cytoplasm of OLI 2, OLI 4, or OLI 14 was detected. In contrast, oligomycin resistance was transferred with the karyoplasts of OLI 14 in karyoplast-cell fusions. Fusions between OLI 14 cells and oligomycin-sensitive cells also produced oligomycin-resistant hybrids. Transfer of oligomycin resistance in the karyoplast-cell and cell-cell fusions were demonstrated at the level of the mitochondrial ATPase. These results indicate that oligomycin resistance in OLI 14 is most likely under nuclear control. Furthermore, nuclear inheritance of oligomycin resistance in a mutant with a modified DCCD-binding protein suggests that the gene for the DCCD-binding protein is encoded in the nucleus of mammalian cells.
Topics: Adenosine Triphosphatases; Animals; Cell Fusion; Cell Nucleus; Drug Resistance; L Cells; Mice; Mitochondria; Mutation; Oligomycins
PubMed: 6459654
DOI: 10.1007/BF01538761 -
Environmental Toxicology and... Jul 2022Microcystin-LR (MC-LR) is a potent cyanotoxin that can reach several organs. However subacute exposure to sublethal doses of MC-LR has not yet well been studied. Herein,...
Microcystin-LR (MC-LR) is a potent cyanotoxin that can reach several organs. However subacute exposure to sublethal doses of MC-LR has not yet well been studied. Herein, we evaluated the outcomes of subacute and sublethal MC-LR exposure on lungs. Male BALB/c mice were exposed to MC-LR by gavage (30 µg/kg) for 20 consecutive days, whereas CTRL mice received filtered water. Respiratory mechanics was not altered in MC-LR group, but histopathology disclosed increased collagen deposition, immunological cell infiltration, and higher percentage of collapsed alveoli. Mitochondrial function was extensively affected in MC-LR animals. Additionally, a direct in vitro titration of MC-LR revealed impaired mitochondrial function. In conclusion, MC-LR presented an intense deleterious effect on lung mitochondrial function and histology. Furthermore, MC-LR seems to exert an oligomycin-like effect in lung mitochondria. This study opens new perspectives for the understanding of the putative pulmonary initial mechanisms of damage resulting from oral MC-LR intoxication.
Topics: Animals; Eating; Lung; Male; Marine Toxins; Mice; Microcystins; Mitochondria; Oligomycins
PubMed: 35598755
DOI: 10.1016/j.etap.2022.103887 -
Biochimica Et Biophysica Acta Jan 1970
Topics: Adipose Tissue; Adipose Tissue, Brown; Animals; Caprylates; Carbon Dioxide; Carbon Isotopes; Cyanides; Depression, Chemical; Drug Synergism; Epinephrine; Female; Glucose; Glycerides; Glycerol; In Vitro Techniques; Lactates; Lipid Metabolism; Microbial Collagenase; Oligomycins; Oxygen Consumption; Phenylhydrazines; Rats; Stimulation, Chemical; Theophylline; Time Factors
PubMed: 4312655
DOI: 10.1016/0005-2728(70)90006-x -
The Biochemical Journal Jun 1997Inhibitors of mitochondrial oxidative metabolism have been proposed to interfere with Ca2+ influx mediated by store-operated channels (SOC), secondary to their effects...
Inhibitors of mitochondrial oxidative metabolism have been proposed to interfere with Ca2+ influx mediated by store-operated channels (SOC), secondary to their effects on ATP production. We assessed SOC activity by 45Ca2+ influx and fluorimetric measurements of free Ca2+ or Mn2+ quench in thapsigargin-treated Chinese hamster ovary cells and Jurkat T-cells, and additionally by electrophysiological measurements of the Ca2+-release-activated Ca2+ current (Icrac) in Jurkat T-cells. Various mitochondrial antagonists were confirmed to inhibit SOC. However, the following evidence supported the proposal that oligomycin, in particular, exerts an inhibitory effect on SOC in addition to its known actions on mitochondria and Na+-pump activity: (i) the concentrations of oligomycin required to inhibit SOC-mediated Ca2+ influx or Icrac (half-inhibitory concentration approximately 2 microM) were nearly 50-fold higher than the concentrations that blocked mitochondrial ATP production; (ii) the rank order of potency of oligomycins A, B and C for decreasing SOC-mediated Ca2+ influx or Icrac differed from that known for inhibition of mitochondrial function; (iii) oligomycin blocked Icrac under voltage clamp and with intracellular Na+ and K+ concentrations fixed by dialysis from the patch pipette, arguing that the effect was not secondary to membrane polarization or pump activity; and (iv) fixing the cytosolic ATP concentration by dialysis from the patch pipette attenuated rotenone- but not oligomycin-mediated inhibition of Icrac. Oligomycin also blocked volume-activated Cl- currents, a profile common to some other known blockers of SOC that are not known mitochondrial inhibitors. These findings raise the possibility that oligomycin interacts directly with SOC, and thus may extend the known pharmacological profile for this type of Ca2+-influx pathway.
Topics: Adenosine Triphosphate; Animals; CHO Cells; Calcium; Cricetinae; Humans; Ion Channels; Ion Transport; Jurkat Cells; Manganese; Mitochondria; Oligomycins
PubMed: 9210424
DOI: 10.1042/bj3240971 -
The Journal of Antibiotics Jul 1987
Topics: Antibiotics, Antineoplastic; Antifungal Agents; HeLa Cells; Humans; Magnetic Resonance Spectroscopy; Oligomycins; Streptomyces
PubMed: 3624067
DOI: 10.7164/antibiotics.40.1053 -
Biochimica Et Biophysica Acta Apr 1991Oligomycin interacts with the Na,K-ATPase by increasing the apparent Na+ affinity in the non-phosphorylated state of the enzyme. This property is used to estimate rate... (Comparative Study)
Comparative Study
Oligomycin interacts with the Na,K-ATPase by increasing the apparent Na+ affinity in the non-phosphorylated state of the enzyme. This property is used to estimate rate constants attributed to oligomycin binding and dissociation reactions with Na,K-ATPase. The rate constants are determined indirectly, employing stop-flow fluorimetry of eosin, the fluorescence of which is a marker for the E1 state of the enzyme, i.e. for Na+ binding. The second-order rate constants derived for oligomycin binding are in the range (6-12).10(4) M-1 s-1 at 6 degrees C for both shark rectal gland and pig kidney enzyme. Rate constants for dissociation of the enzyme-oligomycin complex are about 0.05 s-1 at 6 degrees C. The slow rates of binding and dissociation suggest that oligomycin acts from within the membrane lipid phase rather than from the aqueous phase. The dissociation constant at 6 degrees C for the enzyme-oligomycin complex can be calculated to be about 1 microM for shark enzyme and about 2 microM for kidney enzyme, at pH 7.0 in 2 mM NaCl.
Topics: Animals; Eosine Yellowish-(YS); Kinetics; Membrane Lipids; Oligomycins; Sharks; Sodium-Potassium-Exchanging ATPase; Spectrometry, Fluorescence; Swine
PubMed: 1709053
DOI: 10.1016/0005-2736(91)90408-z -
European Journal of Biochemistry Sep 19801. Oligomycin and dicyclohexylcarbodiimide-sensitive ATPase was isolated from beef-heart mitochondria and treated with 3.5 M NaBr in order to remove F1. The residue,...
1. Oligomycin and dicyclohexylcarbodiimide-sensitive ATPase was isolated from beef-heart mitochondria and treated with 3.5 M NaBr in order to remove F1. The residue, called F0, was found to consist of seven components. Five of these are stained by Coomassie blue after dodecylsulfate-polyacrylamide-gel electrophoresis. Two of them correspond to the oligomycin-sensitivity-conferring protein and coupling factor F6, with apparent molecular weights of 21,000 and 9,400, respectively. Three additional polypeptides of molecular weights 23,000, 10,500 and 8,600 were not identified with known proteins. Two components not stained with Coomassie blue were detected by autoradiography of the gels of F0 preincubated with [14C]dicyclohexylcarbodiimide. These two components probably represent monomeric and oligomeric forms of the dicyclohexylcarbodiimide-binding protein. 2. F0 induced an oligomycin and dicyclohexylcarbodiimide-sensitive enhancement of K+ + valinomycin-driven proton translocation across the membrane of artificial phospholipid vesicles. 3. The interaction of F0 with purified, soluble beef heart F1 was investigated. F0 was capable of binding F1 and conferring oligomycin and dicyclohexylcarbodiimide sensitivity and cold stability on its ATPase activity. Furthermore F0 was found to diminish the specific activity of F1-ATPase. A comparison of these effects at varying F0/F1 ratios shows that F0 binds F1 in both an oligomycin-sensitive and an oligomycin-insensitive manner, and that both types of binding involve a conferral of cold stability and a decrease in specific activity. High F0/F1 ratios favoured in oligomycin-sensitive type of binding, indicating that F1 binds preferentially to oligomycin-sensitivity-conferring sites. Treatment of ATPase complex with trypsin resulted in an F0 with a decreased proportion of oligomycin-sensitivity-conferring binding sites and a diminished ability to lower the specific activity an cold lability of F1. 4. Reconstitution of F0 treated with trypsin and F1, oligomycin-sensitivity-conferring protein and F6 showed that at a constant amount of F1 bound, both oligomycin-sensitivity-conferring protein and F6 increased the oligomycin sensitivity of ATPase activity. It was therefore concluded that both of these coupling factors are involved in the conferral of oligomycin sensitivity. 5. The effect of the order of addition of F1, oligomycin-sensitivity-conferring protein and F6 to F0 on the reconstitution of oligomycin-sensitive ATPase activity, and of F1 and oligomycin-sensitivity-conferring protein to submitochondrial particles on the reconstitution of respiratory control, was investigated. The highest values of oligomycin sensitivity and respiratory control were obtained when F1 was added as the first component, indicating that F1 plays a directing role in the organisation of the components.
Topics: Adenosine Triphosphatases; Animals; Bromides; Carbodiimides; Carrier Proteins; Cattle; Dicyclohexylcarbodiimide; Liposomes; Macromolecular Substances; Membrane Proteins; Mitochondria, Heart; Mitochondrial Proton-Translocating ATPases; Molecular Weight; Oligomycins; Oxidative Phosphorylation Coupling Factors; Proton-Translocating ATPases; Protons; Sodium; Sodium Compounds
PubMed: 6108210
DOI: 10.1111/j.1432-1033.1980.tb04859.x -
Proceedings of the National Academy of... Oct 1977A proteolipid isolated from yeast mitochondrial adenosinetriphosphatase (subunit 9) (ATP phosphohydrolase; EC 3.6.1.3) by chloroform/methanol extraction has been shown...
A proteolipid isolated from yeast mitochondrial adenosinetriphosphatase (subunit 9) (ATP phosphohydrolase; EC 3.6.1.3) by chloroform/methanol extraction has been shown to discharge photo-induced potentials across a planar phospholipid membrane containing bacteriorhodopsin. Oligomycin, a specific inhibitor of oxidative phosphorylation which binds to this protein, allows the potential gradient to be reestablished. When proteolipid was isolated from an oligomycin-resistant strain, ionophoric activity was still obtained but the effect was not reversed by oligomycin. These studies suggest that the hydrophobic subunit-9 polypeptide is the ionophoric component linking ATP synthesis (hydrolysis) with proton translocation.
Topics: Adenosine Triphosphatases; Bacteriorhodopsins; Chemical Phenomena; Chemistry; Drug Resistance, Microbial; Filtration; Fungal Proteins; Ionophores; Lipids; Membranes, Artificial; Mitochondria; Oligomycins; Saccharomyces cerevisiae; Time Factors
PubMed: 144916
DOI: 10.1073/pnas.74.10.4306