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See detailLiver proteomic response to hypertriglyceridemia in human-apolipoprotein C-III transgenic mice at cellular and mitochondrial compartment levels
Ehx, Grégory ULg; Gerin, Stéphanie ULg; Mathy, Grégory et al

in Lipids in Health and Disease (2014), 13

Background: Hypertriglyceridemia (HTG) is defined as a triglyceride (TG) plasma level exceeding 150 mg/dl and is tightly associated with atherosclerosis, metabolic syndrome, obesity, diabetes and acute ... [more ▼]

Background: Hypertriglyceridemia (HTG) is defined as a triglyceride (TG) plasma level exceeding 150 mg/dl and is tightly associated with atherosclerosis, metabolic syndrome, obesity, diabetes and acute pancreatitis. The present study was undertaken to investigate the impact of hypertriglyceridemia on the mitochondrial, sub-mitochondrial and cellular proteomes in the hepatocytes of a hypertriglyceridemic transgenic mouse model overexpressing the human apolipoproteinC-III. Methods: Quantitative comparative proteomics (2D-DIGE) was carried out in both “low-expressor” (LE) and “high-expressor” (HE) mice, respectively exhibiting moderate and severe HTG, to characterize the effect of the TG plasma level on the proteomic response. Results: The mitoproteome analysis revealed the occurrence of a large-scale adaptation in transgenic mice consisting of a general down-regulation of matricial proteins and up-regulation of inner membrane proteins. Remarkably, the magnitude of these proteomic changes appears to strongly depend on the TG plasma level. Altogether, our different analyses indicate that, in HE mice, the capacity of several metabolic pathways is altered to promote the availability of acetyl-CoA, glycerol-3-phosphate, ATP and NADPH for de novo TG biosynthesis. The up-regulation of several cytosolic ROS detoxifying enzymes also tend to confirm that the cytoplasm of HTG mice is subjected to oxidative stress as previously stated. The up-regulation of cytosolic ferritin indicates that iron over-accumulation could take place in the cytosol of HE mice hepatocytes and contribute to (i) enhance oxidative stress and (ii) promote cellular proliferation. Conclusions: The present analyses demonstrate that important TG dose-responsive metabolic adaptations are set up in human apolipoproteinC-III-overexpressing mice. Our results indicate that these adaptations could support the higher TG production rates which have been previously reported in this HTG model, and also suggest that cytosolic oxidative stress may result from FFA over-accumulation, iron overload and enhanced activity of some ROS-producing catabolic enzymes. [less ▲]

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See detailEffects of dietary methylmercury on the Zebrafish (Danio rerio) liver proteome
Brésart, David ULg; Fourdrilis, Séverine; Mathy, Grégory ULg et al

Poster (2010, July 19)

Methylmercury (MeHg) is an aquatic pollutant. It is produced from HgS by the action of sulphate-reducing bacteria and is released in fresh waters. MeHg is bioaccumulated through the trophic chain and is ... [more ▼]

Methylmercury (MeHg) is an aquatic pollutant. It is produced from HgS by the action of sulphate-reducing bacteria and is released in fresh waters. MeHg is bioaccumulated through the trophic chain and is known to cause different health troubles (trembling, memory loss, anemia and kidney deficiency). Toxic exogenous substances, such as MeHg, are transformed by liver’s metabolic pathway, making this the starting point of vertebrate detoxication. Almost 50% of MeHg assimilated in hepatocytes is accumulated in mitochondria (Ware et al.,1975) and It has been suggested that it may uncouples OXPHOS (Mori et al., 2007). The aim of this study was to identify the proteomics modifications of the liver mitochondrial proteome in response to a chronic MeHg intoxication by using the 2D DIGE methodology (Figure 1). Fishes were fed with two different contaminated diets (6.5 and 13.5 µg of MeHgCl / g of dry food.). We have also performed functional assays in order to confirm the MeHg uncoupling effect on Salmo truita liver mitochondria. [less ▲]

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See detailProteomic evolution of s.cerevisiae during chronological aging
Blomme, Arnaud ULg; Mac Cord, Allan ULg; Sluse, Francis ULg et al

Poster (2010, July 19)

Opposite to the replicative aging, which refers to the exponential decline in the capacity of a single cell to divide, chronological aging of the yeast Saccharomyces cerevisiae refers to the time period a ... [more ▼]

Opposite to the replicative aging, which refers to the exponential decline in the capacity of a single cell to divide, chronological aging of the yeast Saccharomyces cerevisiae refers to the time period a yeast cell can survive in a non-dividing state. In 2006, Allen and co-workers reported that yeast cells evolve into two cell types during stationary phase: a high density population defined as quiescent cells (Q) and a low density population defined as non-quiescent (NQ) cells. These two populations mainly differ by their viability, measured as the ability to form colonies when platted on Petri dishes, and can be separated by differential centrifugation on density gradient. In this work, we used the quantitative proteomics technique of 2DDIGE (two Dimensional Differential In-Gel Electrophoresis) to compare the evolution of the yeast cellular soluble proteome during chronological aging. We also checked the impact of the carbon source on stationary-phase cell differentiation. As the ratio of Q/NQ cells is decreasing with time, we have selected three distinct periods: 0 day (32h after outset of yeast culture on glucose, 100% of Q cells), 7 days (50% of Q cells) and 14 days (100% of NQ cells) to realize 3 proteomics comparisons (fig 1). [less ▲]

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See detailDynamics of the Dictyostelium discoideum mitochondrial proteome during vegetative growth, starvation and early stages of development
Czarna, Malgorzata; Mathy, Grégory ULg; Mac Cord, Allan ULg et al

in Proteomics (2010), 9

In this study a quantitative comparative proteomics approach has been used to analyze the D. discoideum mitochondrial proteome variations during vegetative growth, starvation and the early stages of ... [more ▼]

In this study a quantitative comparative proteomics approach has been used to analyze the D. discoideum mitochondrial proteome variations during vegetative growth, starvation and the early stages of development. Application of 2D-DIGE technology allowed the detection of around 2000 protein spots on each two-dimensional gel with 180 proteins exhibiting significant changes in their expression level. In total, 96 proteins (51 unique and 45 redundant) were unambiguously identified. We show that the D. discoideum mitochondrial proteome adaptations mainly affect energy metabolism enzymes (the Krebs cycle, anaplerotic pathways, the oxidative phosphorylation system and energy dissipation), proteins involved in developmental and signalling processes as well as in protein biosynthesis and fate. The most striking observations were the opposite regulation of expression of citrate synthase and aconitase and the very large variation in the expression of the alternative oxidase (AOX) that highlighted the importance of citrate and AOX in the physiology of the development of D. discoideum. Mitochondrial energy states measured in vivo with MitoTracker Orange CMTMRos showed an increase in mitochondrial membrane polarisation during D. discoideum starvation and starvation-induced development. [less ▲]

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See detailProteomic and functional characterization of a Chlamydomonas reinhardtii mutant lacking the mitochondrial alternative oxidase 1
Mathy, Grégory ULg; Cardol, Pierre ULg; Dinant, Monique et al

in Journal of Proteome Research (2010), 9

In the present work we have isolated by RNA interference and characterized at the functional and the proteomic levels a Chlamydomonas reinhardtii strain devoid of the mitochondrial alternative oxidase ... [more ▼]

In the present work we have isolated by RNA interference and characterized at the functional and the proteomic levels a Chlamydomonas reinhardtii strain devoid of the mitochondrial alternative oxidase (AOX). The AOX-deficient strain displays a doubling of the cell volume and biomass without any alteration of the generation time, a significantly higher ROS production, no change in total respiration rate, and a slight decrease of the photosynthesis efficiency. In order to identify the molecular adaptation underlying these phenotypical effects, we carried out a comparative proteomic study at the level of the mitochondrial and cellular soluble proteomes. Our results indicate a strong up-regulation of the ROS scavenging systems and important modifications of proteins involved in the primary metabolism, namely an increase of enzymes involved in anabolic pathways and a concomitant general down-regulation of enzymes of the main catabolic pathways. [less ▲]

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See detailPlasticity of the mitoproteome to nitrogen sources (nitrate and ammonium) in Chlamydomonas reinhardtii: the logic of Aox1 gene localization
Gérin, Stéphanie ULg; Mathy, Grégory ULg; Blomme, Arnaud ULg et al

in Biochimica et Biophysica Acta-Bioenergetics (2010), 1797

Nitrate and ammonium constitute primary inorganic nitrogen sources that can be incorporated into carbon skeletons in photosynthetic eukaryotes. In Chlamydomonas, previous studies and the present one ... [more ▼]

Nitrate and ammonium constitute primary inorganic nitrogen sources that can be incorporated into carbon skeletons in photosynthetic eukaryotes. In Chlamydomonas, previous studies and the present one showed that the mitochondrial AOX is up-regulated in nitrate-grown cells in comparison with ammonium-grown cells. In this work, we have performed a comparative proteomic analysis of the soluble mitochondrial proteome of Chlamydomonas cells growth either on nitrate or ammonium. Our results highlight important proteomics modifications mostly related to primary metabolism in cells grown on nitrate. We could note an up-regulation of some TCA cycle enzymes and a down-regulation of cytochrome c1 together with an up-regulation of l-arginine and purine catabolism enzymes and of ROS scavenging systems. Hence, in nitrate-grown cells, AOX may play a dual role: (1) lowering the ubiquinone pool reduction level and (2) permitting the export of mitochondrial reducing power under the form of malate for nitrate and nitrite reduction. This role of AOX in the mitochondrial plasticity makes logical the localization of Aox1 in a nitrate assimilation gene cluster. [less ▲]

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See detailUncoupling protein 1 inhibition by purine nucleotides is under the control of the endogenous ubiquinone redox state.
Swida-Barteczka, A.; Woyda-Ploszczyca, A.; Sluse, Francis ULg et al

in Biochemical Journal (2009), 424

We studied non-esterified fatty acid-induced uncoupling of heterologously expressed rat UCP1 (uncoupling protein 1) in yeast mitochondria, as well as UCP1 in rat BAT (brown adipose tissue) mitochondria ... [more ▼]

We studied non-esterified fatty acid-induced uncoupling of heterologously expressed rat UCP1 (uncoupling protein 1) in yeast mitochondria, as well as UCP1 in rat BAT (brown adipose tissue) mitochondria. The proton-conductance curves and the relationship between the ubiquinone reduction level and membrane potential were determined in non-phosphorylating BAT and yeast mitochondria. The ADP/O method was applied to determine the ADP phosphorylation rate and the relationship between the ubiquinone reduction level and respiration rate in yeast mitochondria. Our studies of the membranous ubiquinone reduction level in mitochondria demonstrate that activation of UCP1 leads to a purine nucleotide-sensitive decrease in the ubiquinone redox state. Results obtained for non-phosphorylating and phosphorylating mitochondria, as the endogenous ubiquinone redox state was gradually varied by a lowering rate of the ubiquinone-reducing or ubiquinol-oxidizing pathways, indicate that the endogenous ubiquinone redox state has no effect on non-esterified fatty acid-induced UCP1 activity in the absence of GTP, and can only regulate this activity through sensitivity to inhibition by the purine nucleotide. At a given oleic acid concentration, inhibition by GTP diminishes when ubiquinone is reduced sufficiently. The ubiquinone redox state-dependent alleviation of UCP1 inhibition by the purine nucleotide was observed at a high ubiquinone reduction level, when it exceeded 85-88%. [less ▲]

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See detailRegulation of Acanthamoeba castellanii alternative oxidase activity by mutual exclusion of purine nucleotides; ATP's inhibitory effect.
Woyda-ploszczyca, A.; Sluse, Francis ULg; Jarmuszkiewicz, W.

in Biochimica et Biophysica Acta-Bioenergetics (2009), 1787

The effects of different adenine and guanine nucleotides on the cyanide-resistant respiration (i.e. alternative oxidase (AcAOX) activity) of mitochondria from the amoeba A. castellanii mitochondria were ... [more ▼]

The effects of different adenine and guanine nucleotides on the cyanide-resistant respiration (i.e. alternative oxidase (AcAOX) activity) of mitochondria from the amoeba A. castellanii mitochondria were studied. We found that guanine nucleotides activate AcAOX to a greater degree than adenine nucleotides, and that nucleoside monophosphates were more efficient activators than nucleoside di- or triphosphates. The extent of the nucleotides' influence on AcAOX was dependent on the medium's pH and was more pronounced at pH 6.8, which is optimal for AcAOX activity. In contrast to other purine nucleosides, we demonstrate, for the first time, that ATP has an inhibitory effect on AcAOX activity. Since we also observed the inhibition by ATP in the mitochondria of another protozoon, such as Dictyostelium discoideum, and the yeast, Candida maltosa, it may be a regulatory feature common to all purine nucleotide-modulated non-plant AOXs. The physiological importance of this discovery is discussed. Kinetic data show that the binding of GMP (a positive allosteric effector) and the binding of ATP (a negative allosteric effector) to AcAOX are mutually exclusive. ATP's inhibition of the enzyme can be overcome by sufficiently high concentrations of GMP, and conversely, GMP's stimulation can be overcome by sufficiently high concentrations of ATP. However, an approximately three times lower concentration of GMP compared to ATP gives a half maximal effect on AcAOX activity. This is indicative of a higher binding affinity for the positive effector at the same or, at least overlapping, nucleotide-binding sites on AcAOX. These results suggest that AcAOX activity in A. castellanii mitochondria might be controlled by the relative intracellular concentrations of purine nucleotides. [less ▲]

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See detailAtypical Myopathy In Grazing Horses: A First Exploratory Data Analysis
Votion, Dominique ULg; Linden, Annick ULg; Delguste, Catherine ULg et al

in Veterinary Journal (2009), 180(1),

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See detailS13.45 Chlamydomonas reinhardtii mitoproteome adaptation in response to inactivation of the energy-dissipating alternative oxidase 1 by RNA interference
Cloes, Marie ULg; Mathy, Grégory ULg; Cardol, Pierre ULg et al

in Biochimica et Biophysica Acta (BBA) - Bioenergetics, Volume 1777, Supplement 1, 19 July 2008, Page S99 (2008, July 18), 1777(Supplement 1), 99

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See detailMitochondrial comparative proteomics: Strenghts and Pitfalls
Mathy, Grégory ULg; Sluse, Francis ULg

in Biochimica et Biophysica Acta-Bioenergetics (2008), 1977

In this review, we describe the various techniques available to carry out valid comparative proteomics, their advantages and their disadvantages according to the goal of the research. Two-dimensional ... [more ▼]

In this review, we describe the various techniques available to carry out valid comparative proteomics, their advantages and their disadvantages according to the goal of the research. Two-dimensional electrophoresis and 2D-DIGE are compared to shotgun proteomics and SILE. We give our opinion on the best fields of application in the domain of comparative proteomics. We emphasize the usefulness of these new tools, providing mass data to study physiology and mitochondrial plasticity when faced with a specific mitochondrial insufficiency or exogenic stress. We illustrate the subject with results obtained in our laboratory specifying the importance of an approach of comparative proteomics combined from mitochondria and from the cell, which makes it possible to obtain important information on the status of the mitochondrial function at the cellular level. Finally, we draw attention to the dangers of the extrapolation of proteomic data to metabolic flows which requires the greatest care [less ▲]

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See detailDeficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism.
Aragones, Julian; Schneider, Martin; Van Geyte, Katie et al

in Nature Genetics (2008), 40

HIF prolyl hydroxylases (PHD1-3) are oxygen sensors that regulate the stability of the hypoxia-inducible factors (HIFs) in an oxygen-dependent manner. Here, we show that loss of Phd1 lowers oxygen ... [more ▼]

HIF prolyl hydroxylases (PHD1-3) are oxygen sensors that regulate the stability of the hypoxia-inducible factors (HIFs) in an oxygen-dependent manner. Here, we show that loss of Phd1 lowers oxygen consumption in skeletal muscle by reprogramming glucose metabolism from oxidative to more anaerobic ATP production through activation of a Pparalpha pathway. This metabolic adaptation to oxygen conservation impairs oxidative muscle performance in healthy conditions, but it provides acute protection of myofibers against lethal ischemia. Hypoxia tolerance is not due to HIF-dependent angiogenesis, erythropoiesis or vasodilation, but rather to reduced generation of oxidative stress, which allows Phd1-deficient myofibers to preserve mitochondrial respiration. Hypoxia tolerance relies primarily on Hif-2alpha and was not observed in heterozygous Phd2-deficient or homozygous Phd3-deficient mice. Of medical importance, conditional knockdown of Phd1 also rapidly induces hypoxia tolerance. These findings delineate a new role of Phd1 in hypoxia tolerance and offer new treatment perspectives for disorders characterized by oxidative stress. [less ▲]

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See detailMitoproteome plasticity of rat brown adipocytes in response to cold acclimation
Navet, Rachel ULg; Mathy, Grégory ULg; Douette, Pierre ULg et al

in Journal of Proteome Research (2007), 6(1), 25-33

Cold acclimation induces an adaptative increase in respiration in brown adipose tissue (BAT). A comparative analysis by two-dimensional differential in-gel electrophoresis of mitochondrial protein ... [more ▼]

Cold acclimation induces an adaptative increase in respiration in brown adipose tissue (BAT). A comparative analysis by two-dimensional differential in-gel electrophoresis of mitochondrial protein patterns found in rat control and cold-acclimated BAT was performed. A total of 58 proteins exhibiting significant differences in their abundance was unambiguously identified. Proteins implicated in the major catabolic pathways were up-regulated as were ATP synthase and mitofilin. Moreover, these results support the fact that adipocytes can balance their ATP synthesis and their heat production linked to UCP1-sustained uncoupling. [less ▲]

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See detailOxygen consumption of equine articular chondrocytes: Influence of applied oxygen tension and glucose concentration during culture.
Schneider, Nicole ULg; Mouithys-Mickalad, Ange ULg; Lejeune, Jean-Philippe ULg et al

in Cell Biology International (2007), 31

We investigated the oxygen (O2) uptake of equine articular chondrocytes to assess their reactions to anoxia/re-oxygenation. They were cultured under 5% or 21% gas phase O2 and at glucose concentrations of ... [more ▼]

We investigated the oxygen (O2) uptake of equine articular chondrocytes to assess their reactions to anoxia/re-oxygenation. They were cultured under 5% or 21% gas phase O2 and at glucose concentrations of 0, 1.0 or 4.5 g/L in the culture medium (n = 3). Afterwards, the O2 consumption rate of the chondrocytes was monitored (oxymetry) before and after an anoxia period of 25 min. The glucose consumption and lactate release were measured at the end of the re-oxygenation period. The chondrocytes showed a minimal O2 consumption rate, which was hardly changed by anoxia. Independently from the O2 tension, glucose uptake by the cells was about 30% of the available culture medium glucose, thus higher for cells at 4.5 g/L glucose (n = 3). Lactate release was also independent from O2 tension, but lower for cells at 4.5 g/L glucose (n = 3). Our observations indicated that O2 consumption by equine chondrocytes was very low despite a functional mitochondrial respiratory chain, and nearly insensitive to anoxia/re-oxygenation. But the chondrocytes metabolism was modified by an excess of O2 and glucose. [less ▲]

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See detailMuscle energetics in exercising horses
Votion, Dominique ULg; Navet, Rachel ULg; Lacombe, A. et al

in Equine & Comparative Exercise Physiology (2007), 4

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See detailMitochondrial function plasticity in Acanthamoeba castellanii during growth in batch culture.
Czarna, M.; Sluse, Francis ULg; jarmuszkiewicz, W.

in Journal of Bioenergetics & Biomembranes (2007), 39

The alterations in mitochondrial bioenergetics during growth in a batch culture of Acanthamoeba castellanii were studied. The capacity of cytochrome pathway-dependent respiration measured in vitro ... [more ▼]

The alterations in mitochondrial bioenergetics during growth in a batch culture of Acanthamoeba castellanii were studied. The capacity of cytochrome pathway-dependent respiration measured in vitro decreased from the intermediary phase, when cell division slowed down. The pattern of the cytochrome pathway capacity changes was paralleled from the intermediary phase by alterations in the amount of total (and reducible) membranous ubiquinone. These changes were accompanied by a decrease in mitochondrial reactive oxygen species production in vitro (when no energy-dissipating system was active), and almost no change in superoxide dismutase activity and protein level, thus indicating an equivalent need for this enzyme in oxidative stress defence in A. castellanii culture. On the other hand, a decrease in the activity and protein level of alternative oxidase and uncoupling protein was observed in vitro, when cells shifted from the exponential growth phase to the stationary phase. It turned out that the contribution of both energy-dissipating systems in the prevention of mitochondrial reactive oxygen species generation in vivo could lead to its constant level throughout the growth cycle of A. castellanii batch culture. Hence, the observed functional plasticity insures survival of high quality cysts of A. castellanii cells. [less ▲]

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See detailHistory and clinical features of atypical myopathy in horses in Belgium (2000-2005)
Votion, D. M.; Linden, Annick ULg; Saegerman, Claude ULg et al

in Journal of Veterinary Internal Medicine (2007), 21(6, Nov-Dec), 1380-1391

Background: The emergent nature of atypical myopathy or atypical myoglobinuria (AM) necessitates precise description of its clinical and epidemiologic features. Purpose: To define key features of AM to ... [more ▼]

Background: The emergent nature of atypical myopathy or atypical myoglobinuria (AM) necessitates precise description of its clinical and epidemiologic features. Purpose: To define key features of AM to help practitioners recognize the disease and to advise owners to take preventive measures. Animals: Belgian cases of AM confirmed by histology (CC horses; n = 57) from autumn 2000 to spring 2005 were included in the study. Co-grazing horses (Co-G horses; n = 77) that remained free of any abnormal clinical signs constituted a control croup. Methods: History, environmental characteristics, clinical signs, and laboratory results associated with AM were determined by a retrospective case series study. Results: Young horses in poor or normal body condition were found to be at risk for AM. Pastures were characterized by poor natural drainage and vegetation of low nutritional value. Features of AM were seasonal occurrence, apparent link with weather conditions fie, lack of solar radiation with no heavy frost and an excess of precipitation or relative humidity), sudden onset of clinical signs, and rapid death. Evaluation of serum creatine kinase activity indicated severe muscle destruction in CC horses and subclinical disease in a few Co-G horses. Conclusions: The association of AM with specific environmental conditions and individual animals suggests that young horses should not be pastured on bare premises subject to humidity when the weather has been very wet and cold for several days. Management of AM outbreaks should include control of Co-G horses who are apparently healthy. [less ▲]

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See detailSaccharomyces cerevisiae mitoproteome plasticity in response to recombinant alternative ubiquinol oxidase
Mathy, Grégory ULg; Navet, Rachel ULg; Gerkens, Pascal et al

in Journal of Proteome Research (2006), 5(2), 339-348

The energy-dissipating alternative oxidase (AOX) from Hansenula anomala, was expressed in Saccharomyces cerevisiae. The recombinant AOX was functional. A comparative analysis by two-dimensional ... [more ▼]

The energy-dissipating alternative oxidase (AOX) from Hansenula anomala, was expressed in Saccharomyces cerevisiae. The recombinant AOX was functional. A comparative analysis by two-dimensional differential in-gel electrophoresis (2D-DIGE) of mitochondrial protein patterns found in wild-type and recombinant AOX strains was performed. 60 proteins exhibiting a significant difference in their abundance were identified. Interestingly, proteins implicated in major metabolic pathways such as Krebs cycle and amino acid biosynthesis were up-regulated. Surprisingly, an up-regulation of the respiratory-chain complex III was associated with a down-regulation of the ATP synthase complex. [less ▲]

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See detailReduced cardiac output is associated with decreased mitochondrial efficiency in the non-ischemic ventricular wall of the acute myocardial-infarcted dog.
Almsherqi, Z.; McLachlan, C.; Slocinska, M. et al

in Cell Research (2006), 16

Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction (MI). Understanding the mechanisms for acute pump failure is therefore important. The aim of ... [more ▼]

Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction (MI). Understanding the mechanisms for acute pump failure is therefore important. The aim of this study is to examine in an acute MI dog model whether mitochondrial bio-energetic function within non-ischemic wall regions are associated with pump failure. Anterior MI was produced in dogs via ligation of left anterior descending (LAD) coronary artery, that resulted in an infract size of about 30% of the left ventricular wall. Measurements of hemodynamic status, mitochondrial function, free radical production and mitochondrial uncoupling protein 3 (UCP3) expression were determined over 24 h period. Hemodynamic measurements revealed a > 50% reduction in cardiac output at 24 h post infarction when compared to baseline. Biopsy samples were obtained from the posterior non-ischemic wall during acute infarction. ADP/O ratios for isolated mitochondria from non-ischemic myocardium at 6 h and 24 h were decreased when compared to the ADP/O ratios within the same samples with and without palmitic acid (PA). GTP inhibition of (PA)-stimulated state 4 respiration in isolated mitochondria from the non-ischemic wall increased by 7% and 33% at 6 h and 24 h post-infarction respectively when compared to sham and pre-infarction samples. This would suggest that the mitochondria are uncoupled and this is supported by an associated increase in UCP3 expression observed on western blots from these same biopsy samples. Blood samples from the coronary sinus measured by electron paramagnetic resonance (EPR) methods showed an increase in reactive oxygen species (ROS) over baseline at 6 h and 24 h post-infarction. In conclusion, mitochondrial bio-energetic ADP/O ratios as a result of acute infarction are abnormal within the non-ischemic wall. Mitochondria appear to be energetically uncoupled and this is associated with declining pump function. Free radical production may be associated with the induction of uncoupling proteins in the mitochondria. [less ▲]

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See detailMitochondrial UCPs: New insights into regulation and impact
Sluse, Francis ULg; Jarmuszkiewicz, Wieslawa; Navet, Rachel ULg et al

in Biochimica et Biophysica Acta-Bioenergetics (2006), 1757(5-6, Suppl 1), 101

Uncoupling proteins (UCPs) are mitochondrial inner membrane proteins sustaining an inducible proton conductance. They weaken the proton electrochemical gradient built up by the mitochondrial respiratory ... [more ▼]

Uncoupling proteins (UCPs) are mitochondrial inner membrane proteins sustaining an inducible proton conductance. They weaken the proton electrochemical gradient built up by the mitochondrial respiratory chain. Brown fat UCP1 sustains a free fatty acid (FA)-induced purine nucleotide (PN)-inhibited proton conductance. Inhibition of the proton conductance by PN has been considered as a diagnostic of UCP activity. However, conflicting results have been obtained in isolated mitochondria for UCP homologues (i.e., UCP2, UCP3, plant UCP, and protist UCP) where the FFA-activated proton conductance is poorly sensitive to PN under resting respiration conditions. Our recent work clearly indicates that the membranous coenzyme Q, through its redox state, represents a regulator of the inhibition by PN of FFA-activated UCP1 homologues under phosphorylating respiration conditions. Several physiological roles of UCPs have been suggested, including a control of the cellular energy balance as well as the preventive action against oxidative stress. In this paper, we discuss new information emerging from comparative proteomics about the impact of UCPs on mitochondrial physiology, when recombinant UCP1 is expressed in yeast and when UCP2 is over-expressed in hepatic mitochondria during steatosis [less ▲]

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