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At least 721 records · Page 40Linked to original sources
PubMed1990

Evaluation of procedures for assaying oxidative phosphorylation enzyme activities in mitochondrial myopathy muscle biopsies.

The mitochondrial myopathies (MM) are a heterogenous group of neuromuscular diseases associated with abnormal mitochondria and defects in mitochondrial oxidative phosphorylation (OXPHOS). Analysis of a broad spectrum of MM patients has revealed that patients with similar clinical symptoms frequently do not have the same muscle OXPHOS defect. To determine whether some of this variation was due to methodological differences between studies, we have made a detailed survey of OXPHOS enzyme analysis procedures. The coupled OXPHOS assays for Complexes I + III and II + III were found to be variable due to competing reactions and complicated interactions between complexes. These problems were resolved by utilizing specific Complex I and III assays. The muscle mitochondria isolated from surgery patients under general anesthesia and prepared by proteinase digestion were observed to give low and highly variable OXPHOS activities. Mitochondria isolated from muscle biopsies performed under local anesthesia and finely sliced prior to homogenization gave higher and more consistent OXPHOS activities. Assays for Complexes I, III and V required mitochondrial sonication to express maximal activity, but Complex IV was prone to inactivation by excessive mechanical disruption. Mitochondria isolated from frozen muscle or from patients with an OXPHOS disease are more fragile than those isolated from fresh tissue and normal individuals. Hence, Complex IV activity can be preferentially lost from frozen and sonicated myopathy patient samples. These results suggest that variation in muscle OXPHOS analysis techniques may account for some of the discrepancies between clinical manifestations and OXPHOS defects and suggest that no single protocol is sufficient to adequately define the OXPHOS defect in MM patients.

Biopsy↗
PubMedDate not supplied

[Changes in oxidative phosphorylation following exposure to sodium caffeine benzoate].

Sodium caffeine-benzoate at concentrations 6 x 10(-6) M and 6 x 10(-5) M increased the rate of free oxidation of succinic acid in myocardial mitochondria suggesting possibility of uncoupling of respiration and oxidative phosphorylation. The drug stimulates the free flow of electrons in respiratory chain. These phenomena might be responsible for an increase in metabolism and body temperature in patients after the treatment with this drug.

Animals↗
PubMed1998

Effect of bioresmethrin on mitochondrial ultrastructure and oxidative phosphorylation in the flight muscles of Chrysomya albiceps (Wied.) (Diptera: Calliphoridae).

The sublethal effect of bioresmethrin on the ultrastructure, oxidation and phosphorylation of flight muscle mitochondria in the blow fly Chrysomya albiceps which survived treatment of newly formed pupae (0-day old) with 10 micrograms/pupa (LD30) was studied. The ultrastructure of the flight muscle mitochondria was severely deteriorated by treatment with bioresmethrin. The deterioration included disalignment and sometimes destruction of the cristae and vacuolation of mitochondria. The oxidation rate was decreased in treated flies, although the P/O ratio was increased. The present study may indicate that bioresmethrin is neither an uncoupler nor a direct inhibitor of oxidative phosphorylation but may have functioned as an inhibitor of the oxidation rate.

Animals↗
PubMedDate not supplied

[The role of membrane phospholipids in oxidative phosphorylation. A hypothesis of LC-coupling].

The role of lipid (pentadienyl) radicals and Mitchell's "C-elements" was analyzed. The function of the "C-elements" is necessary, but not enough for coupling of oxidation and phosphorylation. It was proposed that oxidative phosphorylation in the mitochondria membrane is the result of a direct coupling, involving participation of the "LC-elements" (where L and C reflect the inductive and capacitive character of the transformation device). The "L-elements" (the short pi-system) are lipid (pentadienyl) radicals formed in polyunsaturated fatty acids of phospholipids.

Adenosine Triphosphate↗
PubMed2002

Interactions of a new 2-styrylchromone with mitochondrial oxidative phosphorylation.

Many chromones, especially those having 2-substituents, manifest a remarkable variety of biological activities, such as the important cytotoxicity against human leukaemia cells, antiallergic, anticancer activities; unfortunately chromones normally disturb mitochondrial bioenergetics. A new 2-styrylchromone has been synthesized by the Baker-Venkataraman method and a classical approach has been used to assess the effects of 2-styrylchromone (3'-allyl-4',5,7-trimethoxy-2-styrylchromone) on rat liver mitochondrial bioenergetic. Mitochondrial respiratory rate and transmembrane potential were measured polarographically using a Clark oxygen electrode and with a selective electrode, respectively. All the disturbance induced by 2-styrylchromone on the enzymatic activities (succinate dehydrogenase, succinate cytochrome c reductase, and cytochrome c oxidase) and in the mitochondrial osmotic volume were determined spectrophotometrically. State 4, state 3, and uncoupled (presence of carbonylcyanide p-trifluoromethoxyphenylhydrazone) respiration rates were decreased by 2-styrylchromone in a concentration-dependent manner. Depression of respiratory activity promoted by 2-styrylchromone is essentially mediated through partial inhibition of succinate cytochrome c reductase. Phosphorylation capacity was strongly depressed as a result of an inhibition on the enzymatic complex (F(0)F(1)-ATPase) and also because of a deleterious effect on the integrity of the mitochondrial membrane, which uncoupled the respiration-generated proton gradient with the proton-driven phosphorylation. The structural integrity of the outside membrane is severely affected since cytochrome c can be released. 2-Styrylchromone uncouples oxidative phosphorylation by an inhibitory action on the redox chain and ATP synthase activity. Additionally, it can release cytochrome c. Cell death can probably result due to the induction of procaspase-9 and other procaspases and by a strong decrease of the available ATP.

Animals↗
PubMed1999

Mechanism of stimulation of glucose transport in response to inhibition of oxidative phosphorylation: analysis with myc-tagged Glut1.

To determine the role of 'translocation' vs. 'activation' of Glut1 in the stimulation of glucose transport in response to inhibition of oxidative phosphorylation, we measured the abundance of myc-tagged Glut1 in plasma membrane of stably transfected Clone 9 cells, a rat liver cell line expressing only the Glut1 isoform. The myc epitope-tag is located between Ile56 and Pro57 in the putative first extracellular loop of Glut1. Under basal conditions, transfected cells expressed approximately 3 fold higher levels of Glut1 and exhibited a approximately 3 fold higher rate of glucose transport than non-transfected cells. To delineate the mechanism mediating the stimulation of glucose transport by a azide we employed two strategies: (1) mild cell surface biotinylation followed by isolation of plasma membranes and quantitation of Glut1 sites in Western blots employing anti-Glut1 and anti-myc antibodies, and (2) quantitative immunofluorescence of myc epitopes in plasma membrane sheets. The rate of glucose transport increased 2.9 +/- 0.5 fold in transfected cells exposed to 5 mM azide for 1 h. Exposure to azide, however, resulted in no significant increase in Glut1 content of plasma membranes using anti-Glut1 or anti-myc antibodies in Western blots (1.0 +/- 0.1 and 0.9 +/- 0.2 fold, respectively; azide/control), and was associated with no detectable increase in immunofluorescence using either anti-Glut1 or anti-myc antibodies (p > 0.1 for both measurements). Treatment of cells with cobalt chloride (employed as a positive control) resulted in marked increases in glucose transport, cell and plasma membrane Glut1 content, and immunofluorescence of plasma membrane sheets (8-10 fold increase in each parameter). We conclude that the stimulation of glucose transport by azide results mainly from activation of Glut1 transporters pre-existing in the plasma membrane.

Animals↗
PubMedDate not supplied

[Oxidative phosphorylation of Krebs cycle substrates in experimental treatment of enterocolitis with cytochrome c].

After administration of exogenous cytochrome c into rats with enterocolitis, caused by salmonellae, tissue respiration and oxidative phosphorylation in presence of succinic, alpha-ketoglutaric, pyruvic and oxaloacetic acids were increased in the liver tissue. Treatment with cytochrome c produced a positive effect on the general state of an organism, led to disappearance of macroscopic alterations in mucosa of small intestine. The data obtained suggest that cytochrome c possesses the positive therapeutic effects in enterocolitis caused by salmonellae.

Animals↗
PubMed2006

Mitochondrial medicine: a metabolic perspective on the pathology of oxidative phosphorylation disorders.

The final steps in the production of adenosine triphosphate (ATP) in mitochondria are executed by a series of multisubunit complexes and electron carriers, which together constitute the oxidative phosphorylation (OXPHOS) system. OXPHOS is under dual genetic control, with communication between the nuclear and mitochondrial genomes essential for optimal assembly and function of the system. We describe the current understanding of the metabolic consequences of pathological OXPHOS defects, based on analyses of patients and of genetically engineered model systems. Understanding the metabolic consequences of OXPHOS disease is of key importance for elucidating pathogenic mechanisms, guiding diagnosis and developing therapies.

Animals↗
PubMed1983

Di-n-butyltindichloride uncouples oxidative phosphorylation in rat liver mitochondria.

In this study di-n-butyltindichloride (DBTC) was found to inhibit alpha-ketoacid-stimulated response of rat liver mitochondria to the addition of ADP and the uncoupler carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (FCCP). The alpha-ketoglutarate oxidation was already inhibited at a level of 0.8 nmol DBTC/mg protein. When succinate was used as substrate together with rotenone, the State 3 and FCCP stimulated oxidation were not inhibited by DBTC. But from a level of 8.3 nmol DBTC/mg protein, the State 4 respiration was increased. It is concluded that in low amounts DBTC specifically blocks alpha-ketoacid dehydrogenases, but higher concentrations of this compound uncouples oxidative phosphorylation. However, this uncoupling will be masked when the NADH production from substrate oxidation is decreased by DBTC as will be in case of alpha-ketoacids.

Adenosine Diphosphate↗
PubMed1978

The mode of inhibition of oxidative phosphorylation by efrapeptin (A23871). Evidence for an alternating site mechanism for ATP synthesis.

Results are presented that confirm and extend earlier findings that efrapeptin is a potent inhibitor of oxidative phosphorylation. Binding of efrapeptin is shown to be reversible, and a dissociation constant for the enzyme-inhibitor complex is estimated to be 10(-8) M under conditions for either ATP synthesis or hydrolysis. Fifty per cent inhibition of the ATP hydrolysis activity of submitochondrial particles is obtained at a ratio of 0.56 mol of inhibitor/mol of enzyme. Studies of efrapeptin binding under pseudo-first order conditions show that the onset of inhibition is first order with respect to efrapeptin. Combined with the inhibition titer, these results indicate that there is one inhibitor binding site per molecule of enzyme. Steady state velocity studies using a substrate regenerating system show that efrapeptin is competitive with both ADP and phosphate during ATP synthesis. However, during ATP hydrolysis, a distinctly different mode of inhibition is indicated with respect to ATP. Data are presented which suggest that ATP promotes the binding of efrapeptin to the enzyme. Indications that efrapeptin is a catalytic site inhibitor make these results difficult to reconcile with a simple mechanistic scheme involving a single independnet catalytic site for ATP synthesis and hydrolysis. Our results are discussed in terms of support for catalytic cooperativity between adjacent subunits as recently proposed by Kayalar et al. (Kayalar, C., Rosing, J., and Boyer, P. D. (1977) J. Biol. Chem. 252, 2486-2491).

Adenosine Triphosphatases↗
PubMed1982

Depletion and recovery of ATP in V79 cells with exposure to inhibitors of glycolysis and oxidative phosphorylation.

Cells of the cultured hamster cell line V79 were labeled with tritiated adenosine and incubated for up to 30 min in the presence of inhibitors of glycolysis and oxidative phosphorylation. These inhibitors were (a) 5 mM KCN plus 5 mM iodoacetate, (b) 5 mM KCN plus 5 mM KF, and (c) 15 mM KCN plus 15 mM KF. The fate of the tritium label was examined during incubation with inhibitors and also during subsequent incubation in growth medium in the absence of inhibitors. The tritiated ATP pool was found to decrease in cells incubated in the presence of any of the inhibitor combinations, but only in the presence of 15 mM KCN plus 15 mM KF was this pool decreased below the level of detection. After cells were incubated with KCN plus KF, a high level of ATP was recovered when the inhibitors were removed. Cells incubated with KCN plus iodoacetate retained depletion levels of ATP. Plating efficiency and trypan blue staining showed that KCN-KF treated cells retained viability, whereas KCN-iodoacetate treated cells did not. Cells were examined for ability to take up tritiated uridine before, during, and after depletion of ATP by incubation in the presence of 15 mM KCN plus 15 mM KF. These cells were found to have a variation in uridine uptake that was related directly to intracellular ATP level. Cells in which the ATP was very low exhibited little or no uridine uptake, whereas cells in which the ATP level was near normal exhibited normal uridine uptake.

Adenosine Triphosphate↗
PubMed1979

Specialized transducing phage lambda carrying the genes for coupling factor of oxidative phosphorylation of Escherichia coli: increased synthesis of coupling factor on induction of prophage lambda asn.

Studies were made of the synthesis of the coupling factor complex (F1--F0) of oxidative phosphorylation after prophage induction of a set of Escherichia coli strains lysogenic for defective transducing phage lambda asn, lambda uncA, or lambda bglC. The transducing phages had been isolated from a strain of E. coli carrying prophage lambda cI857 S7 within the bglB gene located near the unc gene cluster [Miki, T., Hiraga, S., Nagata, T. & Yura, T. (1978) Proc. Natl. Acad. Sci. USA 75, 5099--5103]. When lysogenic cells carrying lambda asn and lambda cI857 S7 were induced at high temperature, synthesis of the F1-ATPase portion of the complex increased to severalfold that of the noninduced cells. In contrast, no increase was observed upon thermoinduction of cells carrying lambda uncA or lambda bglC. The number of membrane sites that could bind purified F1-ATPase also increased significantly upon induction by lambda asn but not by lambda uncA or lambda bglC. In addition, F1-depleted membranes prepared from lambda asn-induced bacteria required more dicyclohexylcarbodiimide to seal the proton pathway than did those from noninduced bacteria. These results strongly suggest that lambda asn carries a set of bacterial genes coding for all the F1 polypeptides (the alpha, beta, gamma, delta, and probably the epsilon subunits) and at least some of the genes involved in formation of F0 polypeptides. Although lambda uncA carries the structural gene (uncA) for the alpha subunit of F1-ATPase, it apparently does not carry the whole set of F1--F0 genes.

Adenosine Triphosphatases↗
PubMed1990

Superoxide radical as electron donor for oxidative phosphorylation of ADP.

When isolated rat heart mitochondria are subject to xanthine/xanthine oxidase generated free radicals, nmol quantities of ADP are phosphorylated to ATP. This effect is proportional to xanthine oxidase concentration, and is relatively independent of ADP concentration. Exogenous superoxide dismutase partially suppresses the phosphorylation. Micromolar concentrations of iron salts completely eliminate the phosphorylation. Catalase has no effect. The likely electron source, then, is superoxide radicals. The reduced minus oxidised spectra of superoxide-bombarded mitochondria show that superoxide enters the electron transport chain by reducing cytochrome c and complex IV. Mitochondria retain their ability to phosphorylate ADP in more traditional ways under the experimental conditions described. Superoxide under physiological conditions in vivo may be a source of electrons for the oxidative phosphorylation of ADP.

Adenosine Diphosphate↗
PubMed1996

Brain energy metabolism, cognitive function and down-regulated oxidative phosphorylation in Alzheimer disease.

Reduced brain glucose utilization in early stages of Alzheimer disease, as measured with in vivo positron emission tomography, reflects potentially reversible down-regulation of gene expression for oxidative phosphorylation within neuronal mitochondria. Such down-regulation may occur when neuronal energy demand is first reduced by synaptic dysfunction or loss.

Alzheimer Disease↗
PubMed1996

Electrophoretic separation of multiprotein complexes from blood platelets and cell lines: technique for the analysis of diseases with defects in oxidative phosphorylation.

A two-dimensional electrophoretic technique combining blue native polyacrylamide gel electrophoresis (BN-PAGE) with Tricine sodium dodecyl sulfate (SDS)-PAGE was previously used for the localization of oxidative phosphorylation (OXPHOS) defects in human diseases starting from biopsy or autopsy tissues (Schägger, H., Electrophoresis 1995, 16, 763-770). In the present work the technique was extended for the resolution of OXPHOS enzymes from platelets and tissue-cultured cells. Silver staining is required to detect the protein subunits of OXPHOS complexes in two-dimensional gels. However, the use of cultured cells has major implications for patients with mitochondrial encephalomyopathies since it will reduce the number of invasive muscle biopsies. The ease of isolating the platelet membrane glycoprotein complex from a few milliliters of blood makes it possible to analyze this complex and its protein subunits in bleeding disorders like Glanzmann's thrombasthenia.

3T3 Cells↗
PubMed1979

Protection and reactivation of oxidative phosphorylation in mitochondria by a stable free-radical prostaglandin polymer (PGBx).

A stable free-radical polymeric derivative of prostaglandin B1 (PGBx) has been synthesized that exhibits regenerative effects on oxidative phosphorylation in aged mitochondria. The molecular weights of the most active preparations fall between 2000 and 2600. PGBx is characterized by a single-line electron spin resonance spectrum that is stable at room temperature. PGBx restores phosphorylating ability and net ATP synthesis in isolated mitochondria aged for 4 days at 0 degrees C and protects against further degradation of phosphorylating activity when such aged mitochondria are preincubated at 28 degrees C in the absence of adenine nucleotide phosphate acceptors. This compound has been reported to exert beneficial effects in vivo in experimental pathological conditions, such as regional ischemia, in which the mitochondria of the ischemic region may have been damaged.

Adenosine Triphosphate↗
PubMed1986

The efficiencies of the component steps of oxidative phosphorylation. II. Experimental determination of the efficiencies in mitochondria and examination of the equivalence of membrane potential and pH gradient in phosphorylation.

In the accompanying article (T.E. Gunter and B.D. Jensen, 1986 Arch. Biochem. Biophys. 248, 289-304), a method is described for measuring the efficiencies of individual steps of the process of oxidative phosphorylation. The results of applying this method to the case of state 3 phosphorylation in rat liver mitochondria are reported here. The rate of energy use (or power use) at the gradient generation, leakage, and phosphorylation steps are reported as efficiencies and energy use factors in tabular form. The limits of the degrees of coupling of the gradient generation and phosphorylation steps are also determined and under the current conditions of measurement these degrees of coupling are found to be quite close to unity. The data can be used to show that the only sets of the stoichiometric parameters noH (the charge/2e- ratio in this case from succinate to oxygen), nPH (the H+/ATP ratio), and nTH (number of protons translocated during substrate-product transport) which are simultaneously consistent with both the laws of thermodynamics and with the current data are 8, 3, 1, and 6, 3, 0. The The efficiency of the phosphorylation step which is independent of noH and nTH averages 80% for the control data analyzed. If noH is 8 (succinate to oxygen), the average value of the efficiency of generation of the electrochemical proton gradient is approximately 91 percent. Since very little power (energy) would then be left over to be coupled in parallel to phosphorylation through some other means of coupling, this would place the electrochemical proton gradient in the direct path of power flow and identify it as "an" intermediate in the process. This would suggest that any other intermediate should be considered as being "in series" with the electrochemical proton gradient. The agents butyrate and propionate have been employed to permit investigation over a range of pH gradient and membrane potential. Both butyrate and propionate decrease the efficiency of generation of the electrochemical proton gradient and increase proton leakage. In addition, butyrate activates electron transport whereas propionate inhibits it. By using butyrate to modify the values of pH gradient and membrane potential, it can be shown that the ratio of the efficiency with which the pH gradient is used in phosphorylation to that with which the membrane potential is used is 1.08 +/- 0.38.

Adenosine Diphosphate↗