Search by property

This page provides a simple browsing interface for finding entities described by a property and a named value. Other available search interfaces include the page property search, and the ask query builder.

List of results

Stride 2013 Eur J Heart Fail + (''AIMS'': Heart failure (HF) with left ven … ''AIMS'': Heart failure (HF) with left ventricular systolic dysfunction (LVSD) is associated with a shift in substrate utilization and a compromised energetic state. Whether these changes are connected with mitochondrial dysfunction is not known. We hypothesized that the cardiac phenotype in LVSD could be caused by reduced mitochondrial oxidative phosphorylation (OXPHOS) capacity and reduced mitochondrial creatine kinase (miCK) capacity. The study aim was to test mitochondrial OXPHOS capacity in LVSD myocardium compared with OXPHOS capacity in a comparable patient group without LVSD.''METHODS AND RESULTS'': Myocardial biopsies were obtained from the left ventricle during cardiac valve or left ventricular assist device (LVAD) surgery. Patients were stratified according to left ventricular ejection fraction (LVEF) into LVSD (LVEF <45%, n = 14) or CONTROL (LVEF >45%, n = 15). Mitochondrial respiration was measured in muscle fibres with addition of non-fatty acid substrates or octanoyl-l-carnitine, a medium chain fatty acid (MCFA). The ''in situ'' enzyme capacity of miCK was determined from APD titrations in the presence or absence of creatine. Maximal OXPHOS capacity with non-fatty acid substrates was lower in the LVSD group compared with the CONTROL group (P ≤ 0.05). ADP sensitivity always increased significantly (P ≤ 0.05) with the addition of creatine, after which the sensitivity was highest (P ≤ 0.05) in LVSD compared with CONTROL. The stimulation of OXPHOS from octanoyl-l-carnitine titrations elicited ∼40% lower respiration in LVSD compared with CONTROL (P ≤ 0.05).''CONCLUSION'': Human LVSD is associated with markedly diminished OXPHOS capacity, particularly in MCFA oxidation. This offers a candidate mechanism for a compromised energetic state and decreased reliance on fatty acid utilization in HF.reased reliance on fatty acid utilization in HF.)
Lou 2013 Cardiovasc Res + (''AIMS'': Infarct-remodelled hearts are le … ''AIMS'': Infarct-remodelled hearts are less amenable to protection against ischaemia/reperfusion. Understanding preservation of energy metabolism in diseased vs. healthy hearts may help to develop anti-ischaemic strategies effective also in jeopardized myocardium.''METHODS AND RESULTS'': Isolated infarct-remodelled/sham Sprague-Dawley rat hearts were perfused in the working mode and subjected to 15 min of ischaemia and 30 min of reperfusion. Protection of post-ischaemic ventricular work was achieved by pharmacological conditioning with sevoflurane. Oxidative metabolism was measured by substrate flux in fatty acid and glucose oxidation using [(3)H]palmitate and [(14)C]glucose. Mitochondrial oxygen consumption was measured in saponin-permeabilized left ventricular muscle fibres. Activity assays of citric acid synthase, hydroxyacyl-CoA dehydrogenase, and pyruvate dehydrogenase and mass spectrometry for acylcarnitine profiling were also performed. Six weeks after coronary artery ligation, the hearts exhibited macroscopic and molecular signs of hypertrophy consistent with remodelling and limited respiratory chain and citric acid cycle capacity. Unprotected remodelled hearts showed a marked decline in palmitate oxidation and acetyl-CoA energy production after ischaemia/reperfusion, which normalized in sevoflurane-protected remodelled hearts. Protected remodelled hearts also showed higher β-oxidation flux as determined by increased oxygen consumption with palmitoylcarnitine/malate in isolated fibres and a lower ratio of C16:1+C16OH/C14 carnitine species, indicative of a higher long-chain hydroxyacyl-CoA dehydrogenase activity. Remodelled hearts exhibited higher PPARα-PGC-1α but defective HIF-1α signalling, and conditioning enabled them to mobilize fatty acids from endogenous triglyceride stores, which closely correlated with improved recovery.''CONCLUSIONS'': Protected infarct-remodelled hearts secure post-ischaemic energy production by activation of β-oxidation and mobilization of fatty acids from endogenous triglyceride stores.acids from endogenous triglyceride stores.)
Carvalho-Kelly 2020 J Bioenerg Biomembr + (''Acanthamoeba castellanii'' is a free-liv … ''Acanthamoeba castellanii'' is a free-living amoeba and the etiological agent of granulomatous amoebic encephalitis and amoebic keratitis. ''A. castellanii'' can be present as trophozoites or cysts. The trophozoite is the vegetative form of the cell and has great infective capacity compared to the cysts, which are the dormant form that protect the cell from environmental changes. Phosphate transporters are a group of proteins that are able to internalize inorganic phosphate from the extracellular to intracellular medium. Plasma membrane phosphate transporters are responsible for maintaining phosphate homeostasis, and in some organisms, regulating cellular growth. The aim of this work was to biochemically characterize the plasma membrane phosphate transporter in ''A. castellanii'' and its role in cellular growth and metabolism. To measure inorganic phosphate (Pi) uptake, trophozoites were grown in liquid PYG medium at 28 °C for 2 days. The phosphate uptake was measured by the rapid filtration of intact cells incubated with 0.5 μCi of 32Pi for 1 h. The Pi transport was linear as a function of time and exhibited Michaelis-Menten kinetics with a Km = 88.78 ± 6.86 μM Pi and Vmax = 547.5 ± 16.9 Pi × h-1 × 10-6 cells. ''A. castellanii'' presented linear phosphate uptake up to 1 h with a cell density ranging from 1 × 105 to 2 × 106 amoeba × ml-1. The Pi uptake was higher in the acidic pH range than in the alkaline range. The oxygen consumption of living trophozoites increased according to Pi addition to the extracellular medium. When the cells were treated with FCCP, no effect from Pi on the oxygen flow was observed. The addition of increasing Pi concentrations not only increased oxygen consumption but also increased the intracellular ATP pool. These phenomena were abolished when the cells were treated with FCCP or exposed to hypoxia. Together, these results reinforce the hypothesis that Pi is a key nutrient for ''Acanthamoeba castellanii'' metabolism.her, these results reinforce the hypothesis that Pi is a key nutrient for ''Acanthamoeba castellanii'' metabolism.)
Votion 2023 MiP2023 + (''Acer pseudoplatanus'' contains toxins re … ''Acer pseudoplatanus'' contains toxins responsible for poisoning in various species [1], including humans [2]. In equids, this intoxication induces an often fatal rhabdomyolysis syndrome known as atypical myopathy (AM); [3]. Blood analysis reveals a severe metabolic disturbance characterised by hyperglycaemia, high triglycerides, and lipid intermediates [4]. Toxins inhibit several steps of the fatty acid β-oxidation cycle that leads to the accumulation of acyl-CoAs in the mitochondria, which are scavenged into acylcarnitines. Also, competitive inhibition of long-chain fatty acid transport into mitochondria results into their accumulation conjugated with carnitine. In addition, inhibition of the catabolic pathway of branched-chain amino acids, particularly leucine, leads to the accumulation of branched acylcarnitines [2; 5]. Acylcarnitines in tissues may explain parts of the pathophysiological process, such as the cardiac myopathy occurring in AM. Also, acylcarnitines accumulation could promote muscle insulin resistance and contribute to the hyperglycaemia observed in AM horses [4]. The disease also results from severe impairment of mitochondrial bioenergetics [6; 7]. In AM, the serum acylcarnitines profile contributes to the diagnosis of the disease, its prognosis and is also a valuable aid in monitoring ongoing metabolic disturbances. In search of new therapeutic approaches for this environmental intoxication, we are currently designing toxicity assays with cultured cells [7] and zebrafish larvae. These models will help us to test different drugs by exploring their ability to prevent metabolic disturbances as indicated by the acylcarnitines profile. Indeed, in both models, the alteration of the acylcarnitine profile can be followed.# Renaud B et al, (2022) Acer pseudoplatanus: A Potential Risk of Poisoning for Several Herbivore Species. https://doi.org/10.3390/toxins14080512# Tanaka K, Isselbacher KJ, Shih V (1972) Isovaleric and -methylbutyric acidemias induced by hypoglycin A: mechanism of Jamaican vomiting sickness. https://doi.org/10.1126/science.175.4017.69 # Votion DM, Serteyn D (2008) Equine atypical myopathy: a review. https://doi.org/10.1016/j.tvjl.2008.02.004# Boemer F, Detilleux J, Cello C, Amory H, Marcillaud-Pitel C, Richard E, van Galen G, van Loon G, Lefere L, Votion DM (2017) Acylcarnitines profile best predicts survival in horses with atypical myopathy. https://doi.org/10.1371/journal.pone.0182761# Wouters CP et al, (2021) Metabolomic Signatures Discriminate Horses with Clinical Signs of Atypical Myopathy from Healthy Co-grazing Horses. https://doi.org/10.1021/acs.jproteome.1c00225# Lemieux H et al, (2016) Mitochondrial function is altered in horse atypical myopathy. https://doi.org/10.1016/j.mito.2016.06.005 # Kruse CJ, Stern D, Mouithys-Mickalad A, Niesten A, Art T, Lemieux H, Votion DM (2021) In Vitro Assays for the Assessment of Impaired Mitochondrial Bioenergetics in Equine Atypical Myopathy. https://doi.org/10.3390/life11070719e Atypical Myopathy. https://doi.org/10.3390/life11070719 )
Chen 2020 Biochim Biophys Acta Mol Basis Dis + (''Ad libitum'' high-fat diet (HFD) induces … ''Ad libitum'' high-fat diet (HFD) induces obesity and skeletal muscle metabolic dysfunction. Liver kinase B1 (LKB1) regulates skeletal muscle metabolism by controlling the AMP-activated protein kinase family, but its importance in regulating muscle gene expression and glucose tolerance in obese mice has not been established. The purpose of this study was to determine how the lack of LKB1 in skeletal muscle (KO) affects gene expression and glucose tolerance in HFD-fed, obese mice. KO and littermate control wild-type (WT) mice were fed a standard diet or HFD for 14 weeks. RNA sequencing, and subsequent analysis were performed to assess mitochondrial content and respiration, inflammatory status, glucose and insulin tolerance, and muscle anabolic signaling. KO did not affect body weight gain on HFD, but heavily impacted mitochondria-, oxidative stress-, and inflammation-related gene expression. Accordingly, mitochondrial protein content and respiration were suppressed while inflammatory signaling and markers of oxidative stress were elevated in obese KO muscles. KO did not affect glucose or insulin tolerance. However, fasting serum insulin and skeletal muscle insulin signaling were higher in the KO mice. Furthermore, decreased muscle fiber size in skmLKB1-KO mice was associated with increased general protein ubiquitination and increased expression of several ubiquitin ligases, but not muscle ring finger 1 or atrogin-1. Taken together, these data suggest that the lack of LKB1 in skeletal muscle does not exacerbate obesity or insulin resistance in mice on a HFD, despite impaired mitochondrial content and function and elevated inflammatory signaling and oxidative stress.Copyright © 2020. Published by Elsevier B.V.right © 2020. Published by Elsevier B.V.)
Oliveira 2022 Abstract Bioblast-Aedes + (''Aedes aegypti'' females are natural vect … ''Aedes aegypti'' females are natural vectors of important arboviruses including Dengue, Zika and yellow fever. Mosquitoes activate innate immune response signaling pathways upon infection, which target the pathogens and limit their propagation. Despite the beneficial effects of immune activation for insect vectors, there are phenotypic costs that ultimately affect their fitness. However, the underlying mechanisms that mediate these fitness costs remain poorly understood. Given the high energy required to mount a proper immune response, we hypothesized that systemic activation of innate immunity would impair flight muscle mitochondrial function, compromising tissue energy demand and flight activity. Here, we investigated the dynamic effects of activation of innate immunity by intra-thoracic zymosan injection on ''A. aegypti'' flight muscle mitochondrial metabolism. Zymosan injection significantly increased defensin expression in fat bodies in a time-dependent manner and ultimately affecting induced flight activity. Although oxidant levels in flight muscle were hardly altered, [[P-L net OXPHOS capacity |''P''-''L'' net OXPHOS capacity]] ([[OXPHOS capacity |OXPHOS capacity ''P'']] minus [[LEAK respiration |LEAK respiration ''L'']]; ADP→ATP-linked) and [[ET capacity |electron transfer capacity ''E'']] (maximal mitochondrial oxygen consumption rates) supported by pyruvate & proline were significantly reduced at 24 h upon zymosan injection. These effects were parallel to significant and specific reductions in Complex I activity upon zymosan treatment. Finally, the magnitude of defensin up-regulation negatively correlated with maximal, ATP-linked, and NADH&proline-linked respiratory rates ''P'' and ''E'' in flight muscles. Despite strong reductions were observed in proline and [[E-P excess capacity |''E''-''P'' excess capacity]] 24 h upon zymosan injection, this effect was not correlated to the magnitude of innate immune response activation. Collectively, we demonstrate that activation of innate immunity in fat body strongly associates to reduced flight muscle Complex I activity with direct consequences on mitochondrial physiology and dispersal. Remarkably, our results indicate that a trade-off between dispersal and immunity exists in an insect vector, underscoring the potential consequences of disrupted flight muscle mitochondrial energy metabolism on arbovirus transmission.drial energy metabolism on arbovirus transmission.)
Gaviraghi 2019 Anal Biochem + (''Aedes aegypti'' is the most important an … ''Aedes aegypti'' is the most important and widespread vector of arboviruses, including dengue and zika. Insect dispersal through the flight activity is a key parameter that determines vector competence, and is energetically driven by oxidative phosphorylation in flight muscle mitochondria. Analysis of mitochondrial function is central for a better understanding of cellular metabolism, and is mostly studied using isolated organelles. However, this approach has several challenges and methods for assessment of mitochondrial function in chemically-permeabilized tissues were designed. Here, we described a reliable protocol to assess mitochondrial physiology using mechanically permeabilized flight muscle of single ''A. aegypti'' mosquitoes in combination with high-resolution respirometry. By avoiding the use of detergents, high respiratory rates were obtained indicating that substrate access to mitochondria was not limited. This was confirmed by using selective inhibitors for specific mitochondrial substrates. Additionally, mitochondria revealed highly coupled, as ATP synthase or adenine nucleotide translocator inhibition strongly impacted respiration. Finally, we determined that pyruvate and proline induced the highest respiratory rates compared to other substrates tested. This method allows the assessment of mitochondrial physiology in mosquito flight muscle at individual level, and can be used for the identification of novel targets aiming rational insect vector control.Copyright © 2019. Published by Elsevier Inc.right © 2019. Published by Elsevier Inc.)
Lou 2012 Cardiovasc Res + (''Aims:'' Infarct-remodeled hearts are les … ''Aims:'' Infarct-remodeled hearts are less amenable to protection against ischemia-reperfusion. Understanding preservation of energy metabolism in diseased versus healthy hearts may help to develop anti-ischemic strategies also effective in jeopardized myocardium.''Methods and Results:'' Isolated infarct-remodeled/sham Sprague-Dawley rat hearts were perfused in the working mode and subjected to 15 min of ischemia and 30 min of reperfusion. Protection of postischemic ventricular work was achieved by pharmacologic conditioning with sevoflurane. Oxidative metabolism was measured by substrate flux in fatty acid and glucose oxidation using [(3)H]palmitate and [(14)C]glucose. Mitochondrial oxygen consumption was measured in saponin-permeabilized left ventricular muscle fibers. Activity assays of citric acid synthase, hydroxyacyl-CoA dehydrogenase, and pyruvate dehydrogenase and mass spectrometry for acylcarnitine profiling were also performed. Six weeks after coronary artery ligation, hearts exhibited macroscopic and molecular signs of hypertrophy consistent with remodeling and limited respiratory chain and citric acid cycle capacity. Unprotected remodeled hearts showed a marked decline in palmitate oxidation and acetyl-CoA energy production after ischemia/reperfusion, which normalized in sevoflurane-protected remodeled hearts. Protected remodeled hearts also showed higher β-oxidation flux as determined by increased oxygen consumption with palmitoylcarnitine/malate in isolated fibers and a lower ratio of C16:1+C16OH/C14 carnitine species, indicative of a higher long-chain hydroxyacyl-CoA dehydrogenase activity. Remodeled hearts exhibited higher PPARα-[[PGC-1α]] but defective HIF-1α signaling and conditioning enabled them to mobilize fatty acids from endogenous triglyceride store, which closely correlated with improved recovery.''Conclusions:'' Protected infarct-remodeled hearts secure postischemic energy production by activation of β-oxidation and mobilization of fatty acids from endogenous triglyceride stores.acids from endogenous triglyceride stores.)
Furlanetto 2014 Thesis University of Parana + (''Araucaria angustifolia'' is listed as cr … ''Araucaria angustifolia'' is listed as critically endangered by International Union for Conservation of Nature (IUCN) red list of threatened species. The development and propagation of this species is strongly affected by abiotic stress, such as the temperature variation. We previously shown the activation of plant uncoupling mitochondrial protein (PUMP) in embryogenic ''A. angustifolia'' cells submitted to cold stress, an effect associated to oxidative stress. In this work, we advanced in these studies by submitting these cells to cold stress (4 ± 1°C for 24h or 48h) and evaluating the cellular and mitochondrial response associated to oxidative stress, namely: the H2O2 levels, the activity of antioxidant enzymes and lipid peroxidation. In mitochondria from these cells were evaluated the activity of NAD(P)H alternative dehydrogenases and mitochondrial permeability transition (MPT). The cold stress did not affect the morphology and viability of embryogenic ''A. angustifolia'' cells; however, increased the H2O2 levels by ~35% (at 24h and 48h) and lipid peroxidation by ~15% and 30% after 24h and 48h of stress, respectively. The activity of catalase was decreased by ~20% after 48h of cold stress while ascorbate peroxidase (APx) and dehydroascorbate redutase (DHAR) activities were increased by ~100% and ~64%, respectively. For the cells exposition to cold stress by 24h only dehydroascorbate redutase (MDHAR) had the activity increased by ~172%. Glutathione reductase (GR) and superoxide dismutase activities remained unchanged under both stress conditions. In mitochondria, the cold stress promoted a significant inhibition of external alternative NAD(P)H dehydrogenases (~40% at 24h of stress and ~65% at 48h of stress) while the mitochondrial permeability transition (MPT) was slightly inhibited in both, 24h and 48h of stress. The cold stress induces the oxidative stress in embryogenic ''A. angustifolia'' cells, which result in up-regulation of the enzymatic defense mainly the activation of gluthatione-ascorbate cycle in a compensatory way to the inhibition of catalase and external NAD(P)H dehydrogenases. These results contribute to understanding the pathway to overcoming the cold in this gymnosperm and are important for the development of conservation methods of this species such as ''in vitro'' micropropagation.ies such as ''in vitro'' micropropagation.)
Kucera 2012 J Gastroenterol Hepatol + (''BACKGROUND AND AIM'' Acetaminophen overd … ''BACKGROUND AND AIM'' Acetaminophen overdose is the most frequent cause of acute liver failure. Non-alcoholic fatty liver disease is the most common chronic condition of the liver. The aim was to assess whether non-alcoholic steatosis sensitizes rat liver to acute toxic effect of acetaminophen.''METHODS'' Male Sprague-Dawley rats were fed a standard diet (ST-1, 10% kcal fat) and high-fat gelled diet (HFGD, 71% kcal fat) for 6 weeks and then acetaminophen was applied in a single dose (1 g/kg body weight). Animals were killed 24, 48 and 72 h after acetaminophen administration. Serum biochemistry, activities of mitochondrial complexes, hepatic malondialdehyde, reduced and oxidized glutathione, triacylglycerol and cholesterol contents, and concentrations of serum and liver cytokines (TNF-α, TGF-β1) were measured and histopathological samples were prepared.''RESULTS'' The degree of liver inflammation and hepatocellular necrosis were significantly higher in HFGD fed animals after acetaminophen administration. Serum markers of liver injury were elevated only in acetaminophen treated HFGD fed animals. Concentration of hepatic reduced glutathione and ratio of reduced/oxidized glutathione were decreased in both ST-1 and HFGD groups at 24 h after acetaminophen application. Mild oxidative stress induced by acetaminophen was confirmed by measurement of malondialdehyde. Liver content of TNF-α was not significantly altered, but hepatic TGF-β1 was elevated in acetaminophen treated HFGD rats. We did not observe acetaminophen-induced changes in activities of respiratory complexes I, II, and IV and activity of caspase-3.''CONCLUSION'' Liver from rats fed HFGD is more susceptible to acute toxic effect of acetaminophen, compared to non-steatotic liver.minophen, compared to non-steatotic liver.)

(''BACKGROUND AND AIM'' Acetaminophen overdose is the most frequent cause)

Cumero 2012 Br J Pharmacol + (''Background & Purpose'': T1AM is a th … ''Background & Purpose'': T1AM is a thyronamine derivative of thyroid hormone acting as a signalling molecule via non-genomic effectors and can reach intracellular targets. In light of the importance of F0F1-ATPsynthase as a target in drug development, T1AM interaction with the enzyme is demonstrated by its effects on the activity and a model of binding locations is depicted.''Experimental Approach'': Kinetic analyses were performed on F0F1-ATPsynthase in sub-mitochondrial particles and soluble F1-ATPase. Activity assays and immunodetection of the inhibitor protein IF1 were used and combined with molecular docking analyses. ''In situ'' respirometric analysis of T1AM effect was investigated on H9c2 cardiomyocytes.''Key Results'': T1AM is a non-competitive inhibitor of F0F1-ATPsynthase whose binding is mutually exclusive with that of the inhibitors IF1 and aurovertin B. Distinct T1AM binding sites are consistent with results from both kinetic and docking analyses: at low nanomolar concentrations, T1AM binds to a high affinity-region likely located within the IF1 binding site, causing IF1 release; at higher concentrations, T1AM binds to a low affinity-region likely located within the aurovertin binding cavity and inhibits enzyme activity. Low nanomolar concentrations of T1AM elicit in cardiomyocytes an increase in ADP-stimulated mitochondrial respiration indicative for an activation of F0F1-ATPsynthase consistent with displacement of endogenous IF1, thereby reinforcing the ''in vitro'' results.''Conclusions & Implications'': The T1AM effects upon F0F1-ATPsynthase are twofold: IF1 displacement and enzyme inhibition. By targeting F0F1-ATPsynthase within mitochondria T1AM might affect cell bioenergetics with a positive effect on mitochondrial energy production at low endogenous concentration. T1AM putative binding locations overlapping with IF1 and aurovertin binding sites are depicted.lt;/sub>-ATPsynthase within mitochondria T1AM might affect cell bioenergetics with a positive effect on mitochondrial energy production at low endogenous concentration. T1AM putative binding locations overlapping with IF1 and aurovertin binding sites are depicted.)
Usui 2012 Eur J Anaes + (''Background and Goal of Study'': Anesthet … ''Background and Goal of Study'': Anesthetics have been demonstrated to inhibit mitochondrial function in animal models, an effect that could be related to neurological sequelae of prolonged or excessive anesthesia in man. It has been proposed that toxicity of anesthetic agents could be caused by inhibition of the electron transport system. In this study, using high-resolved respirometry of human blood cells, the objective was to evaluate the influence of commonly used anesthetic agents in a wide concentration range on mitochondrial oxygen consumption in platelets.''Materials and Methods'': Platelets samples were isolated from healthy volunteers and were rapidly analyzed by [[high-resolution respirometry]] using an Oroboros-2k Oxygraph. Platelets were exposed to propofol (5-150 μg/mL), sevoflurane (0.4-8 mmol/L) and midazolam (0.1-20 μg/mL). Mitochondria were stimulated with complex-specific substrates and inhibitors. Statistical analysis were performed using one way ANOVA with post hoc Dunnett’s test and were compared to a separate control group (''N''＝20). Informed consent was received from all participants and the study was approved by the ethical committee of Tokyo Medical University.''Results and Discussion'': Within the therapeutic concentration-range of the investigated agents, no apparent inhibition of respiratory capacity was noted. Rather, at therapeutic concentrations, significant increases in mitochondrial respiratory parameters were detected for sevoflurane and propofol. Dose-dependent inhibition of respiration was found in the presence of high doses of propofol (30 μg/mL and above) and sevoflurane (1.6 mmol/L and above). The respiratory inhibition was more prominent for Complex I respiration as compared to Complex II-supported respiration. For midazolam no significant effects were noted at the concentration range investigated.''Conclusion'': In freshly isolated and permeabilized human platelets, the commonly used anesthetics sevoflurane and propofol stimulate mitochondrial respiratory capacity at clinically relevant concentrations. At higher concentrations, these agents displayed a dose-dependent inhibition of Complex I and II-supported respiration. The increased respiratory capacity induced by sevoflurane and propofol might be beneficial and the inhibition of respiration could be relevant to situations of prolonged or excessive exposure, especially in situations of tissue accumulation of these anesthetics. tissue accumulation of these anesthetics.)
Goncalves 2009 PLoS One + (''Background'': Hematophagy poses a challe … ''Background'': Hematophagy poses a challenge to blood-feeding organisms since products of blood digestion can exert cellular deleterious effects. Mitochondria perform multiple roles in cell biology acting as the site of aerobic energytransducing pathways, and also an important source of reactive oxygen species (ROS), modulating redox metabolism. Therefore, regulation of mitochondrial function should be relevant for hematophagous arthropods. Here, we investigated the effects of blood-feeding on flight muscle (FM) mitochondria from the mosquito ''Aedes aegypti'', a vector of dengue and yellow fever.''Methodology/Principal Findings'': Blood-feeding caused a reversible reduction in mitochondrial oxygen consumption, anevent that was parallel to blood digestion. These changes were most intense at 24 h after blood meal (ABM), the peak ofblood digestion, when oxygen consumption was inhibited by 68%. Cytochromes ''c'' and ''a+a3 '' levels and cytochrome c oxidase activity of the electron transport chain were all reduced at 24 h ABM. Ultrastructural and molecular analyses of FM revealed that mitochondria fuse upon blood meal, a condition related to reduced ROS generation. Consistently, BF induced a reversible decrease in mitochondrial H2O2 formation during blood digestion, reaching their lowest values at 24 h ABM where a reduction of 51% was observed.''Conclusion'': Blood-feeding triggers functional and structural changes in hematophagous insect mitochondria, which mayrepresent an important adaptation to blood feeding.ct mitochondria, which may represent an important adaptation to blood feeding.)
Favory 2006 Am J Respir Crit Care Med + (''Background'': Results from both animal a … ''Background'': Results from both animal and human being studies provide evidence that inhalation of concentrations of carbon monoxide (CO) at around 100 ppm has antiinflammatory effects. These low levels of CO are incriminated in ischemic heart diseases experienced by cigarette smokers and, in some cases, from air pollution. Although neurologic mechanisms have been investigated, the effects of CO on cardiovascular function are still poorly understood.''Methods and Results'': The effects of CO (250 ppm; 90 min) inhalation on myocardial function were investigated in isolated heart of rats killed immediately, and 3, 24, 48, and 96 h after CO exposure. CO exposure at 250 ppm resulted in an arterial carboxyhemoglobin (HbCO) level of approximately 11%, which was not associated with changes in mean arterial pressure and heart rate. CO exposure induced coronary perfusion pressure increases, which were associated with endothelium-dependent and -independent vascular relaxation abnormalities. CO-induced coronary vascular relaxation perturbations were observed in the presence of increased heart contractility. Spontaneous peak to maximal Ca2+-activated left ventricular pressure ratio was markedly increased in CO-exposed rats, indicating increases in myofilament calcium sensitivity. Heart cyclic guanosine monophosphate/cAMP ratio and myocardial permeabilized fiber respiration (complex intravenous activity) were reduced in CO-exposed rats, which lasted after 48 h of reoxygenation in air.''Conclusions'': These findings suggest that CO deteriorates heart oxygen supply to utilization and potentially may induce myocardial hypoxia through mechanisms that include increased oxygen demand due to increased contractility, reduced coronary blood flow reserve, and cardiomyocyte respiration inhibition.low reserve, and cardiomyocyte respiration inhibition.)
Votion 2012 PLoS One + (''Background'': Within the animal kingdom, … ''Background'': Within the animal kingdom, horses are among the most powerful aerobic athletic mammals. Determination of muscle respiratory capacity and control improves our knowledge of mitochondrial physiology in horses and high aerobic performance in general.We applied high-resolution respirometry and multiple [[substrate-uncoupler-inhibitor titration]] protocols to study mitochondrial physiology in small (1.0 – 2.5 mg) permeabilized muscle fibres sampled from triceps brachii of healthy horses. Oxidative phosphorylation ([[OXPHOS]]) capacity [pmol O2∙s-1∙mg-1 wet weight] in the NADH&succinate-pathway (NS, combined [[CI&II]]-linked substrate supply: glutamate&malate&succinate) increased from 77±18 in overweight horses to 103±18, 122±15, and 129±12 in untrained, trained andcompetitive horses (''N'' = 3, 8, 16, and 5, respectively). Similar to human muscle mitochondria, equine OXPHOS capacity was limited by the phosphorylation system to 0.85±0.10 (''N'' = 32) of electron transfer capacity, independent of fitness level. In 15 trained horses, OXPHOS capacity increased from 119±12 to 134±37 when pyruvate was included in the NS-substrate cocktail. Relative to this maximum OXPHOS capacity, NADH-linked OXPHOS capacities (N) were only 50 % with glutamate&malate, 64 % with pyruvate&malate, and 68 % with pyruvate&glutamate&malate, and ~78 % with succinate&rotenone (S). OXPHOS capacity with glutamate&malate increased with fitness relative to NS-supported ET capacity from a flux control ratio of 0.38 to 0.40, 0.41 and 0.46 in overweight to competitive horses, whereas the S/NS substrate control ratio remained constant at 0.70. Therefore, the apparent deficit of the N- over S-pathway capacity was reduced with physical fitness. The scope of mitochondrial density-dependent OXPHOS capacity and the density-independent (qualitative) increase of N-respiratory capacity with increased fitness open up new perspectives of integrative and comparative mitochondrial respiratory physiology.tory capacity with increased fitness open up new perspectives of integrative and comparative mitochondrial respiratory physiology.)
Luevano-Martinez 2019 Fungal Biol + (''Blastocladiella emersonii'' is an early … ''Blastocladiella emersonii'' is an early diverging fungus of the phylum Blastocladiomycota. During the life cycle of the fungus, mitochondrial morphology changes significantly, from a fragmented form in sessile vegetative cells to a fused network in motile zoospores. In this study, we visualize these morphological changes using a mitochondrial fluorescent probe and show that the respiratory capacity in zoospores is much higher than in vegetative cells, suggesting that mitochondrial morphology could be related to the differences in oxygen consumption. While studying the respiratory chain of the fungus, we observed an antimycin A and cyanide-insensitive, salicylhydroxamic (SHAM)-sensitive respiratory activity, indicative of a mitochondrial alternative oxidase (AOX) activity. The presence of AOX was confirmed by the finding of a ''B. emersonii'' cDNA encoding a putative AOX, and by detection of AOX protein in immunoblots. Inhibition of AOX activity by SHAM was found to significantly alter the capacity of the fungus to grow and sporulate, indicating that AOX participates in life cycle control in ''B. emersonii''.Copyright © 2018 British Mycological Society. Published by Elsevier Ltd. All rights reserved.ed by Elsevier Ltd. All rights reserved.)
Thorgersen 2022 Front Microbiol + (''Brevibacillus massiliensis'' strain phR … ''Brevibacillus massiliensis'' strain phR is an obligately aerobic microbe that was isolated from human feces. Here, we show that it readily takes up tungsten (W), a metal previously associated only with anaerobes. The W is incorporated into an oxidoreductase enzyme (BmWOR) that was purified from native biomass. BmWOR consists of a single 65 kDa subunit and contains a single W-pyranopterin cofactor and a single [4Fe-4S] cluster. It exhibited high aldehyde-oxidizing activity with very high affinities (apparent ''K''m < 6 μM) for aldehydes common in the human gut and in cooked foods, including furfural, propionaldehyde, benzaldehyde and tolualdehyde, suggesting that BmWOR plays a key role in their detoxification. ''B. massiliensis'' converted added furfural to furoic acid when grown in the presence of W, but not in the presence of the analogous element molybdenum. ''B. massiliensis'' ferredoxin (BmFd) served as the electron acceptor (apparent ''K''m < 5 μM) for BmWOR suggesting it is the physiological electron carrier. Genome analysis revealed a Fd-dependent rather than NADH-dependent Complex I, suggesting that WOR not only serves a detoxification role but its aldehyde substrates could also serve as a source of energy. BmWOR is the first tungstoenzyme and the first member of the WOR family to be obtained from a strictly aerobic microorganism. Remarkably, BmWOR oxidized furfural in the presence of air (21 % O2, v/v) but only if BmFd was also present. BmWOR is the first characterized member of the Clade 83 WORs, which are predominantly found in extremely halophilic and aerobic archaea (Clade 83A), with many isolated from food sources, while the remaining bacterial members (Clade 83B) include both aerobes and anaerobes. The potential advantages for microbes found in foods and involved in human gut health that harbor O2-resistant WORs, including in ''Bacillus'' and ''Brevibacillus'' based-probiotics, are discussed.Brevibacillus'' based-probiotics, are discussed.)
Wyss 2016 Abstract IOC116 + (''By author request, this abstract is not made available online.'')
Piller 1995 J Exp Biol + (''Callinectes sapidus'' and ''C. similis'' … ''Callinectes sapidus'' and ''C. similis'' co-occur in estuarine waters above 15 salinity. ''Callinectes sapidus'' also inhabits more dilute waters, but ''C. similis'' is rarely found below 15 . Previous work suggests that ''C. sapidus'' may be a better hyperosmoregulator than ''C. similis''. In this study, energy metabolism and the levels of transport-related enzymes in excised gills were used as indicators of adaptation to low salinity. Oxygen consumption rates and mitochondrial cytochrome content of excised gills increased in both species as acclimation salinity decreased, but to a significantly greater extent in ''C. similis'' gills. In addition, ''C. similis'' gills showed the same levels of carbonic anhydrase and Na+/K+-ATPase activities and the same degree of enzyme induction during low-salinity adaptation as has been reported for ''C. sapidus'' gills. However, hemolymph osmolality and ion concentrations were consistently lower in ''C. similis'' at low salinity than in ''C. sapidus''. Therefore, although gills from low-salinity-acclimated ''C. similis'' have a higher oxygen consumption rate and more mitochondrial cytochromes than ''C. sapidus'' gills and the same level of transport-related enzymes, ''C. similis'' cannot homeostatically regulate their hemolymph to the same extent as ''C. sapidus.''ymph to the same extent as ''C. sapidus.'')
Dufour 2013 Appl Environ Microbiol + (''Campylobacter jejuni'' is a widespread p … ''Campylobacter jejuni'' is a widespread pathogen responsible for most of the food-borne gastrointestinal diseases in Europe. The use of natural antimicrobial molecules is a promising alternative to antibiotic treatments for pathogen control in the food industry. Isothiocyanates are natural antimicrobial compounds, which also display anti-cancer activity. Several studies described the chemoprotective effect of isothiocyanates on eukaryotic cells, but the antimicrobial mechanism is still poorly understood.We investigated the early cellular response of ''C. jejuni'' to benzylisothiocyanate by both transcriptomic and physiological approaches. The transcriptomic response of ''C. jejuni'' to benzylisothiocyanate showed upregulation of heat shock response genes and an impact on energy metabolism. The oxygen consumption was progressively impaired by benzylisothiocyanate treatment as revealed by high-resolution respirometry, while the ATP content increased soon after benzylisothiocyanate exposition, which suggests a shift in the energy metabolism balance. Finally, benzylisothiocyanate induced intracellular protein aggregation. These results indicate that benzylisothiocyanate affects ''C. jejuni'' by targeting proteins, resulting in the disruption of major metabolic processes and eventually leading to cell death.sses and eventually leading to cell death.)