Pseudomonas aeruginosa lipopolysaccharide: an uncoupler of mitochondrial oxidative phosphorylation

1975 ◽  
Vol 21 (6) ◽  
pp. 877-883 ◽  
Author(s):  
G. Gordon Greer ◽  
F. H. Milazzo
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Oxygen Uptake ◽  
Oxidative Phosphorylation ◽  
Respiratory Control ◽  
Substrate Oxidation ◽  
Respiratory Control Ratio ◽  
Mitochondrial Oxidative Phosphorylation

The addition of Pseudomonas aeruginosa KCIIR LPS to respiring mitochondria stimulated the rate of substrate oxidation, reduced the respiratory control ratio, stimulated oxygen uptake in state 4, and released the inhibition imposed upon state 3 by atractyloside. It was concluded that LPS acted as an uncoupler of oxidative phosphorylation and that it produced effects similar to those observed with the classical uncoupler 2,4-dinitrophenol.

Effects of 6-hydroxydopamine on oxidative phosphorylation of mitochondria from rat striatum, cortex, and liver

1988 ◽  
Vol 66 (3) ◽  
pp. 376-379 ◽  
Author(s):  
J. H. Thakar ◽  
M. N. Hassan
Keyword(s):  
Oxidative Phosphorylation ◽  
Incubation Medium ◽  
Respiratory Control ◽  
Rat Striatum ◽  
Respiratory Control Ratio ◽  
Chemical Sympathectomy ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Consumption Ratio ◽  
6 Hydroxydopamine

The catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) has been used to produce cardiac chemical sympathectomy as well as a model of parkinsonism. Several mechanisms have been proposed to explain its cytotoxicity, including the productions of quinones, hydrogen peroxide, and free radicals by autooxidation and the uncoupling of mitochondrial oxidative phosphorylation. We have observed that 6-OHDA at a concentration of 0.05 mM rapidly consumes oxygen from the mitochondrial incubation medium but does not affect oxidative phosphorylation in the mitochondria from rat striatum, cortex, and liver. At the higher concentration of 0.5 mM, 6-OHDA consumes all of the available oxygen from the incubation medium. Mitochondria exposed to this concentration of 6-OHDA show decreases in the respiratory control ratio and adenosine triphosphate synthesis as measured by the consumption ratio of ADP to oxygen. Thus, only the higher (0.5 mM) concentration of 6-OHDA, which produces anoxia in vitro, also causes mitochondrial damage.

scholarly journals Improved method for isolation of coupled mitochondria of Araucaria angustifolia (Bert.) O. Kuntze

2004 ◽  
Vol 47 (6) ◽  
pp. 873-879 ◽  
Author(s):  
André Bellin Mariano ◽  
Leonardo Kovalhuk ◽  
Caroline Valente ◽  
Juliana Maurer-Menestrina ◽  
Adaucto Bellarmino Pereira-Netto ◽  
...  
Keyword(s):  
Oxygen Uptake ◽  
Oxidative Phosphorylation ◽  
Embryogenic Callus ◽  
Respiratory Control ◽  
Mitochondrial Bioenergetics ◽  
Respiratory Control Ratio ◽  
Araucaria Angustifolia ◽  
Improved Method ◽  
First Time

A method for the isolation of coupled mitochondria from the callus of Araucaria angustifolia is described for the first time. Mitochondria were isolated from embryogenic callus of A. angustifolia. They were metabolically active, able to sustain oxidative phosphorylation as shown by respiratory control ratio values, which were about 2.4 when respiring on succinate as substrate. Oxygen uptake experiments, using freeze-thawed disrupted mitochondria, showed the presence of alternative rotenone-insensitive NAD(P)H dehydrogenases, which were stimulated by Ca2+. The procedure now described for the isolation of A. angustifolia mitochondria is an important new tool, allowing the investigation of mitochondrial bioenergetics and metabolism and physiology of plants.

scholarly journals Alteration of Pseudomonas aeruginosa respiration by 4-(1-adamantyl)-phenol derivative

Biologija ◽  
2018 ◽  
Vol 64 (3) ◽  
Author(s):  
Daria M. Dudikova ◽  
Nina O. Vrynchanu ◽  
Valentyna I. Nosar
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Oxygen Consumption ◽  
Oxidative Phosphorylation ◽  
Respiratory Chain ◽  
Structural Integrity ◽  
Respiratory Control ◽  
Endogenous Respiration ◽  
Phenol Derivative ◽  
Succinate Oxidation ◽  
Intact Cells

Derivatives of 4-(1-adamantyl)-phenol are a promising class of antimicrobials affecting the structural integrity and functions of the bacterial cell membrane. The functioning of Pseudomonas aeruginosa respiratory chain and related system of oxidative phosphorylation was investigated before and after treatment with a derivative of 4-(1-adamantyl)-phenol (compound KVM-97). Oxygen consumption was measured polarographically with a Clark-type oxygen electrode. KVM-97 was tested at 0.5× and 1.0× MIC (minimum inhibitory concentration). Specific substrates of the respiratory chain (either 3.0 mM glutamate with 2.0 mM malonate or 3.0 mM succinate with 5.0 μM rotenone) were used. All reactions were stimulated by addition of ADP (0.2 mmol). It was found that at tested concentrations, KVM-97 inhibited the endogenous respiration and substrate oxidation in P. aeruginosa cells. The inhibiting effect was dose-dependent and more pronounced with succinate oxidation rather than glutamate oxidation. The respiratory control index value (RCI) in compound-treated cells was in average 1.5 times lower compared to the intact cells. The decrease in the RCI was related to changing the oxygen uptake rates in state 3 and state 4, which indicate the uncoupling of respiration and oxidative phosphorylation. The data obtained showed that 4-(1-adamantyl)-phenol derivative inhibits oxygen consumption and has uncoupling effects in P. aeruginosa cells.

scholarly journals The effect of sulodexide on placental mitochondria function in rats with experimental preeclampsia

2016 ◽  
Vol 62 (5) ◽  
pp. 572-576 ◽  
Author(s):  
T.A. Popova ◽  
V.N. Perfilova ◽  
G.A. Zhakupova ◽  
V.E. Verovsky ◽  
O.V. Ostrovskij ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Respiratory Control ◽  
Negative Control ◽  
Urinary Protein ◽  
Control Group ◽  
Respiratory Control Ratio ◽  
Pregnant Rats ◽  
Pronounced Increase ◽  
Uncoupling Of Oxidative Phosphorylation

Substitution of drinking water for 1.8% NaCl in pregnant rats caused a pronounced increase in arterial pressure by 24,3% and urinary protein by 117% to day 21 of pregnancy. State 4 respiration of isolated placental mitochondria in the group of negative control was 3- and 1.5-fold higher with malate/glutamate and succinate as substrates than in placental mitochondria isolated from uncomplicated pregnant animals. This led to a decrease of the respiratory control ratio. These results suggest that development of experimental preeclampsia is accompanied by mitochondrial dysfunction through uncoupling of oxidative phosphorylation. Daily administration of sulodexide to females with experimental preeclampsia (EP) per os at a dose of 30 LE during the whole period of gestation decreased manifestations of the disease as evidenced by a slight increase in blood pressure (by 8,6%) and less pronounces increase in urinary protein (by 58,9%). Sulodexide decreased development of mitochondrial dysfunction in EP rats as shown a decrease of non-stimulated ADP respiration with malate/glutamate and succinate (4.5- and 2.5-fold, respectively) as compared with the negative control group and the corresponding increase in the respiratory control ratio (2.5- and 1.5-fold, respectively). Thus, sulodexide reduces uncoupling of oxidative phosphorylation and enhances the functional activity of mitochondria in EP animals, possibly due to its antioxidant and endotelioprotective effects.

Respiration and oxidative phosphorylation by muscle and heart mitochondria of hamsters with hereditary myocardiopathy and polymyopathy

1968 ◽  
Vol 46 (4) ◽  
pp. 323-329 ◽  
Author(s):  
Klaus Wrogemann ◽  
M. C. Blanchaer
Keyword(s):  
Skeletal Muscle ◽  
Oxidative Phosphorylation ◽  
Histological Examination ◽  
Creatine Phosphokinase ◽  
Respiratory Control ◽  
Isolation Procedure ◽  
Heart Mitochondria ◽  
Respiratory Control Ratio ◽  
Skeletal Muscle Mitochondria ◽  
Serum Creatine Phosphokinase

Mitochondria isolated from skeletal muscle and heart of normal Syrian hamsters and from hamsters of the BIO 14.6 myopathic strain aged 97–124 days were studied. Histological examination of the tissues and serum creatine phosphokinase determinations established that the disease was active in the dystrophic animals. In the mitochondrial isolation procedure the minced tissue was incubated before homogenization in a mannitol–sucrose–EDTA medium containing a proteinase (Nagarse). Polarographic estimations with pyruvate–malate as substrate, in the presence and absence of ADP, indicated that the rate of O2 uptake, ADP/O ratio, and respiratory control ratio (state 3 to 4 transition) of the heart mitochondria did not suffer significantly between the normal and myopathic groups. The findings with the skeletal muscle mitochondria were similar. L-α-Glycerophosphate oxidation also was not affected by the myopathy but the rate of NADH oxidation was 35% slower in the heart mitochondria of the BIO 14.6 strain.

OXIDATIVE PHOSPHORYLATION BY MUSCLE MITOCHONDRIA OF DYSTROPHIC MICE

1967 ◽  
Vol 45 (8) ◽  
pp. 1271-1278 ◽  
Author(s):  
Klaus Wrogemann ◽  
M. C. Blanchaer
Keyword(s):  
Skeletal Muscle ◽  
Oxidative Phosphorylation ◽  
Respiratory Control ◽  
Laboratory Strain ◽  
Adenosine Diphosphate ◽  
Isolation Procedure ◽  
Respiratory Control Ratio ◽  
Differential Centrifugation ◽  
Dystrophic Mice ◽  
Phosphorylation Rate

Oxidative phosphorylation was studied in mitochondria isolated from the skeletal muscle of control and dystrophic mice of the Jackson Laboratory strain 129/Re, aged 32–104 days. The isolation procedure included a preliminary incubation of the muscle minced in a medium containing a proteinase (Nagarse) followed by gentle homogenization and differential centrifugation. Polarographic estimations in the presence and absence of adenosine diphosphate (ADP) indicated that the rate of oxygen uptake, ADP/0 ratio, respiratory control ratio, and phosphorylation rate were not significantly different in the mitochondria isolated from control and dystrophic mice. Bovine serum albumin increased the ADP/0 and respiratory control ratios, but the values for the control and dystrophic preparations again did not differ significantly in the presence of albumin.

Alterations of mitochondria in liver but not in heart homogenates after treatment of rats with benznidazole

2014 ◽  
Vol 33 (10) ◽  
pp. 1066-1070 ◽  
Author(s):  
DA Rendon
Keyword(s):  
Oxidative Phosphorylation ◽  
Day Treatment ◽  
Respiratory Control ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Inner Mitochondrial Membrane ◽  
Oral Gavage ◽  
Daily Dose ◽  
Female Wistar Rats ◽  
Proton Leakage ◽  
Liver Homogenates

The mitochondrial oxidative phosphorylation system was studied in liver and heart homogenates after treatment of rats with benznidazole. The drug was given by oral gavage to adult female Wistar rats for 9 consecutive days (100 mg benznidazole/kg body weight as a daily dose). The mitochondrial state 4 and state 3 respiration rates, respiratory control, efficiency of oxidative phosphorylation (ADP/O), and ATPsynthase activity were assayed. The results showed that according to all these parameters, the mitochondria in cardiac homogenates were not affected in the rats treated with benznidazole. By contrast, mitochondria in the liver homogenates of drug-treated rats were altered, showing decreased respiratory control and a lower coefficient of ADP/O as a result of an increase in the state 4 respiration rate. These data indicate the possibility of production of an uncoupling factor leading to increased proton leakage through the inner mitochondrial membrane as a result of a 9-day treatment of rats with benzonidazole. The obtained experimental data might at least partly explain the nature of benznidazole toxicity in the liver treated with benznidazole.

Age-related increase in mitochondrial proton leak and decrease in ATP turnover reactions in mouse hepatocytes

1998 ◽  
Vol 275 (2) ◽  
pp. E197-E206 ◽  
Author(s):  
Mary-Ellen Harper ◽  
Shadi Monemdjou ◽  
Jon J. Ramsey ◽  
Richard Weindruch
Keyword(s):  
Oxygen Consumption ◽  
Oxidative Phosphorylation ◽  
Metabolic Control ◽  
Respiratory Control ◽  
Substrate Oxidation ◽  
Membrane Lipid ◽  
Proton Leak ◽  
Control Analysis ◽  
Atp Turnover ◽  
Age Related

Age-related changes in mitochondria, including decreased respiratory control ratios and altered mitochondrial inner membrane lipid composition, led us to study oxidative phosphorylation in hepatocytes from old (30 mo) and young (3 mo) male C57BL/J mice. Top-down metabolic control analysis and its extension, elasticity analysis, were used to identify changes in the control and regulation of the three blocks of reactions constituting the oxidative phosphorylation system: substrate oxidation, mitochondrial proton leak, and the ATP turnover reactions. Resting oxygen consumption of cells from old mice was 15% lower ( P < 0.05) than in young cells. This is explained entirely by a decrease in oxygen consumption supporting ATP turnover reactions. At all values of mitochondrial membrane potential assessed, the proportion of total oxygen consumption used to balance the leak was greater in the old cells than in the young cells. Metabolic control coefficients indicate a shift in control over respiration and phosphorylation away from substrate oxidation toward increased control by leak and by ATP turnover reactions. Control of the actual number of ATP molecules synthesized by mitochondria for each oxygen atom consumed by the ATP turnover and leak reactions was greater in old than in young cells, showing that efficiency in older cells is more sensitive to changes in these two blocks of reactions than in young cells.

scholarly journals Studies on the Energy Metabolism of Human Leukocytes

Blood ◽  
1967 ◽  
Vol 30 (2) ◽  
pp. 168-175 ◽  
Author(s):  
JOHN M. FOSTER ◽  
MARY L. TERRY ◽  
Harriet Gunther
Keyword(s):  
Energy Metabolism ◽  
Electron Transport ◽  
Oxidative Phosphorylation ◽  
Respiratory Control ◽  
Endogenous Respiration ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Human Leukocytes ◽  
Endogenous Activity ◽  
Stimulation Of

Abstract 1. Oxidative phosphorylation has been studied in mitochondrial preparations from human leukocytes, using recently developed methods for homogenization, measuring respiration, and assaying for ATP. 2. Appreciable stimulation of both respiration and phosphorylation was limited to 3 substrates: succinate, malate, and α-glycerophosphate. The effects of other substrates were minimal. 3. The stimulating effects of these 3 substrates responded to inhibitors in a manner typical of mitochondrial oxidative phosphorylation. There was also considerable endogenous activity which, however, was insensitive to inhibitors. It is concluded the endogenous respiration and phosphorylation are not associated with electron transport. Subtracting their values from the data, P/O ratios consistent with good phosphorylation with the 3 substrates are obtained. 4. Studies with oligomycin and dinitrophenol suggest the presence of respiratory control. This indicates the mitochondria are intact. It is concluded that in the intact leukocyte the mitochondria are a major source of ATP.

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