Components Of Electron Transport System Research Articles

Brain Region and Cell Compartment Dependent Regulation of Electron Transport System Components in Huntington's Disease Model Mice.

Huntington’s disease (HD) is a rare hereditary neurodegenerative disorder characterized by multiple metabolic dysfunctions including defects in mitochondrial homeostasis and functions. Although we have recently reported age-related changes in the respiratory capacities in different brain areas in HD mice, the precise mechanisms of how mitochondria become compromised in HD are still poorly understood. In this study, we investigated mRNA and protein levels of selected subunits of electron transport system (ETS) complexes and ATP-synthase in the cortex and striatum of symptomatic R6/2 mice. Our findings reveal a brain-region-specific differential expression of both nuclear and mitochondrial-encoded ETS components, indicating defects of transcription, translation and/or mitochondrial import of mitochondrial ETS components in R6/2 mouse brains.

Compared salt tolerance of five local wheat (Triticum aestivum L.) cultivars of Albania based on morphology, pigment synthesis and glutathione content

Abstract Stressful saline concentrations in soils affect photosynthesis by damaging pigments, photosystems, components of electron transport system, and enzymes involved in the process. Plants respond through very complex stress adaptation mechanisms including proteome modulation, alterations in pigment content, cell osmotic adjustment and control of ion and water homeostasis mechanisms, which stabilize cytosolic glutathione redox potential, etc. The level of plant sensitivity depends on salt toxicity levels, growth stage, physiological and genetic factors. With aim the investigation of the salinity tolerant cultivars, and for the elucidation of mechanisms underlying this complex biological process, here we analyze the impact of four NaCl concentrations (0-50-100-200mM) in growth parameters (root, shoot and leaves length), pigment content (chla, chlb, carotenoids), and GSH content, during seedling of five bread wheat (Triticum aestivum L.) cultivars in modified Hoagland solutions. Based on biometric parameters, pigment synthesis and GSH content cultivar Nogal is salt-sensitive (growth and pigments reduced); cultivar Viktoria is medium-tolerant (growth partially impaired, pigments constant), cultivar Toborzo and cultivar Suba are medium-tolerant (growth partially impaired, pigments increased), cultivar Dajti salt-tolerant (growth partially impaired/ leaves developed, pigments increased). Quantity of GSH in response to different levels of salinity is cultivar specific, and time of exposure to salinity is in negative correlation to GSH content for all investigated cultivars.

Hyperoxia Decreases Glycolytic Capacity, Glycolytic Reserve and Oxidative Phosphorylation in MLE-12 Cells and Inhibits Complex I and II Function, but Not Complex IV in Isolated Mouse Lung Mitochondria

High levels of oxygen (hyperoxia) are frequently used in critical care units and in conditions of respiratory insufficiencies in adults, as well as in infants. However, hyperoxia has been implicated in a number of pulmonary disorders including bronchopulmonary dysplasia (BPD) and adult respiratory distress syndrome (ARDS). Hyperoxia increases the generation of reactive oxygen species (ROS) in the mitochondria that could impair the function of the mitochondrial electron transport chain. We analyzed lung mitochondrial function in hyperoxia using the XF24 analyzer (extracellular flux) and optimized the assay for lung epithelial cells and mitochondria isolated from lungs of mice. Our data show that hyperoxia decreases basal oxygen consumption rate (OCR), spare respiratory capacity, maximal respiration and ATP turnover in MLE-12 cells. There was significant decrease in glycolytic capacity and glycolytic reserve in MLE-12 cells exposed to hyperoxia. Using mitochondria isolated from lungs of mice exposed to hyperoxia or normoxia we have shown that hyperoxia decreased the basal, state 3 and state3 μ (respiration in an uncoupled state) respirations. Further, using substrate or inhibitor of a specific complex we show that the OCR via complex I and II, but not complex IV was decreased, demonstrating that complexes I and II are specific targets of hyperoxia. Further, the activities of complex I (NADH dehydrogenase, NADH-DH) and complex II (succinate dehydrogenase, SDH) were decreased in hyperoxia, but the activity of complex IV (cytochrome oxidase, COX) remains unchanged. Taken together, our study show that hyperoxia impairs glycolytic and mitochondrial energy metabolism in in tact cells, as well as in lungs of mice by selectively inactivating components of electron transport system.

Photosynthesis under stressful environments: An overview

Stressful environments such as salinity, drought, and high temperature (heat) cause alterations in a wide range of physiological, biochemical, and molecular processes in plants. Photosynthesis, the most fundamental and intricate physiological process in all green plants, is also severely affected in all its phases by such stresses. Since the mechanism of photosynthesis involves various components, including photosynthetic pigments and photosystems, the electron transport system, and CO2 reduction pathways, any damage at any level caused by a stress may reduce the overall photosynthetic capacity of a green plant. Details of the stress-induced damage and adverse effects on different types of pigments, photosystems, components of electron transport system, alterations in the activities of enzymes involved in the mechanism of photosynthesis, and changes in various gas exchange characteristics, particularly of agricultural plants, are considered in this review. In addition, we discussed also progress made during the last two decades in producing transgenic lines of different C3 crops with enhanced photosynthetic performance, which was reached by either the overexpression of C3 enzymes or transcription factors or the incorporation of genes encoding C4 enzymes into C3 plants. We also discussed critically a current, worldwide effort to identify signaling components, such as transcription factors and protein kinases, particularly mitogen-activated protein kinases (MAPKs) involved in stress adaptation in agricultural plants.

Insulin prevents mitochondrial generation of H2O2 in rat brain

The mitochondrial electron transport system (ETS) is a main source of cellular ROS, including hydrogen peroxide (H2O2). The production of H2O2 also involves the mitochondrial membrane potential (ΔΨm) and oxygen consumption. Impaired insulin signaling causes oxidative neuronal damage and places the brain at risk of neurodegeneration. We evaluated whether insulin signaling cross-talks with ETS components (complexes I and FoF1ATP synthase) and ΔΨm to regulate mitochondrial H2O2 production, in tissue preparations from rat brain. Insulin (50 to 100ng/mL) decreased H2O2 production in synaptosomal preparations in high Na+ buffer (polarized state), stimulated by glucose and pyruvate, without affecting the oxygen consumption. In addition, insulin (10 to 100ng/mL) decreased H2O2 production induced by succinate in synaptosomes in high K+ (depolarized state), whereas wortmannin and LY290042, inhibitors of the PI3K pathway, reversed this effect; heated insulin had no effect. Insulin decreased H2O2 production when complexes I and FoF1ATP synthase were inhibited by rotenone and oligomycin respectively suggesting a target effect on complex III. Also, insulin prevented the generation of maximum level of ∆Ψm induced by succinate. The PI3K inhibitors and heated insulin maintained the maximum level of ∆Ψm induced by succinate in synaptosomes in a depolarized state. Similarly, insulin decreased ROS production in neuronal cultures. In mitochondrial preparations, insulin neither modulated H2O2 production or oxygen consumption. In conclusion, the normal downstream insulin receptor signaling is necessary to regulate complex III of ETS avoiding the generation of maximal ∆Ψm and increased mitochondrial H2O2 production.

Physiological responses to temperature and haeme synthesis modifiers in earthworm Lumbricus terrestris (Annelida: Oligochaeta)

Earthworms (Lumbricus terrestris) acclimated at 2° and 6°C above their average habitat temperature (10°C) had respectively 15 and 40% higher rate of respiration than those at habitat temperature. At 14°C, the rate of respiration and blood hemoglobin (Hb) concentration both increased by ∼60 and 50%, respectively, of the values at habitat temperature. At higher temperatures the rate of respiration and Hb synthesis started decreasing. At 20-23°C, the respiration and Hb concentration decreased respectively by about 85% and 35% of that at 14°C. Decrease in blood Hb concentration at higher temperatures appeared to be due to the lowering of the activity of blood enzyme δ-aminolaevulinic acid dehydratase (ALAD). Exposure of 20-23°C-acclimated pale worms to ALAD inhibitor (lead), lowered the already compromised rate of respiration and blood Hb concentration; while exposure to hexachlorobenzene (HCB, inducer of haeme synthesis) and ferric chloride (enhancer of haeme synthesis) did not overcome the inhibitory effect of high temperature on Hb synthesis. At 20-23°C the affinity of Hb for oxygen also decreased as indicated by the lowering of oxy-Hb (HbO) concentration in blood. The lowering of concentration of blood Hb and its affinity for oxygen may lower the amount of oxygen delivered to cells, which may limit the level of aerobic metabolism (glycolysis, oxidative phosphorylation), as indicated by an increase in blood glucose concentration and a decrease in in vitro activities of mitochondrial electron transport system components (ETS) namely NADH-cytochrome c reductase, succinate dehydrogenase, cytochrome c oxidase, and ATPases. Although the oxygen concentration in air, at sea level, does not decrease significantly from 6° to 20-23°C (lack of hypoxia), lowering of both Hb and HbO concentrations by high temperature may cause significant hypoxemia. The latter may lead to inhibition of the activity of muscle mitochondrial respiratory enzymes (ETS). The resulting inhibition of ATP synthesis and hydrolysis may cause deficit of energy needed for peristalsis/fictive locomotion of body and heart muscles (as indicated by a decrease in heart rate) to facilitate diffusion and transport of gases. The upper critical temperature (20-23°C) also slows down the heart rate and causes hyperosmotic stress (hypovolemia). Thus, a rise in soil temperature above 18°C, which inhibits Hb synthesis, Hb oxygenation, and mitochondrial ETS activity, and slows down the heart rate and causes hyperosmotic stress, can make this and higher temperatures lethal to populations of these earthworms, especially in the presence of metabolic inhibitors and respiratory poisons.

Rip1 enhances methylmercury toxicity through production of reactive oxygen species (ROS) in budding yeast

Reactive oxygen species (ROS) produced by mitochondria are potentially involved in the manifestation of methylmercury toxicity. However, the molecular mechanism underlying methylmercury toxicity remains poorly understood. We examined susceptibility to methylmercury in yeast strains that each lacked one of components of the mitochondrial electron transport system. Resistance to methylmercury was exhibited only by yeast that lacked Rip1, a component of electron transport system complex III. Resistance to methylmercury in Rip1-deficient yeast was independent of the activity of electron transport system complex III. Also, ROS levels induced by methylmercury in Rip1-deficient yeast were significantly lower than in wild-type yeast. Thus, Rip1 is potentially involved in ROS production through an as-yet unknown mechanism that is independent of the activity of electron transport system complex III, thereby enhancing methylmercury toxicity.

Aberrant regulation of choline metabolism by mitochondrial electron transport system inhibition in neuroblastoma cells

Anomalous choline metabolic patterns have been consistently observed in vivo using Magnetic Resonance Spectroscopy (MRS) analysis of patients with neurodegenerative diseases and tissues from cancer patient. It remains unclear; however, what signaling events may have triggered these choline metabolic aberrancies. This study investigates how changes in choline and phospholipid metabolism are regulated by distinct changes in the mitochondrial electron transport system (ETS). We used specific inhibitors to down regulate the function of individual protein complexes in the ETS of SH-SY5Y neuroblastoma cells. Interestingly, we found that dramatic elevation in the levels of phosphatidylcholine metabolites could be induced by the inhibition of individual ETS complexes, similar to in vivo observations. Such interferences produced divergent metabolic patterns, which were distinguishable via principal component analysis of the cellular metabolomes. Functional impairments in ETS components have been reported in several central nervous system (CNS) diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD); however, it remains largely unknown how the suppression of individual ETS complex function could lead to specific dysfunction in different cell types, resulting in distinct disease phenotypes. Our results suggest that the inhibition of each of the five ETS complexes might differentially regulate phospholipase activities within choline metabolic pathways in neuronal cells, which could contribute to the overall understanding of mitochondrial diseases.

Isolation and characterization of genes coding for cytochrome b5 and cytochrome- b5 reductase

Cytochrome b, and NADH-dependent cytochrome 6,reductase (EC 1.6.2.2) are components of electron transport systems. In the endoplasmic reticulum of liver and many other tissues the proteins are involved in the desaturation of fatty acids (Oshino & Sato, 1971) and in the cytochrome I-’150-mediated metabolism of endogenous compounds such as steroids, and of foreign compounds including many drugs, carcinogens and environmental pollutants (Ortiz de Montellano, 1986). In the cytosol of mature erythrocytes, cytochrome b, and cytochrome-b, reductase are present as smaller water-soluble species that are responsible for the reduction of methaemoglobin (Hultquist & Passon, 197 1). The inherited disorder methaemoglobinaemia can be due to a homozygous deficiency of erythrocyte cytochrome-b, reductase (Scott & Griffith, 1959; Hultquist & Passon, 1971) or, in at least one case, to a deficiency of cytochrome b, (Hegesh et al., 1986). In this paper we report the isolation and characterization of rat and human cDNA and rat genomic DNA clones coding for cytochrome b,, and a human cDNA clone coding for cytochrome h,-reductase.

In vivo effects of nitrogen dioxide on membrane constituents in lung and liver of rats

When rats were exposed to 10 ppm NO 2 for 7 days, the succinate-cytochrome c reductase activity, the rate-limiting step of mitochondrial succinoxidase, of the liver decreased progressively, reaching 77% ( P < 0.01) of the control level by the fifth day. By contrast, this activity was gradually increased by a 10-day exposure to 4 ppm NO 2 and reached 1.14-fold that of the control level at the seventh day. A reduction in the components of electron-transport systems in liver microsomes was found during exposure to NO 2 at both concentrations. This reduction was preferential for components of drug-metabolizing systems. The NADPH-cytochrome c reductase activity and the cytochrome P-450 content were decreased to 82% ( P < 0.05) and 76% ( P < 0.05), respectively, at the fifth day of exposure to 10 ppm NO 2. Exposure to 4 ppm NO 2 also caused a significant decrease in the NADPH-cytochrome c reductase and the cytochrome P-450 content, which were lowered to 84% ( P < 0.05) of the control level at the fourth and seventh days, respectively. Reduction in these components appears to occur even at the concentration of 0.4 ppm at the seventh day. Alterations in the components of mitochrondria and microsomes of the lung were considerably different from those of the liver. The protein content of the lung increased to 1.18 ( P < 0.05)- and 1.14 ( P < 0.05)-fold that of the control during exposure to 10 and 4 ppm NO 2, respectively. The succinate-cytochrome c reductase activity showed a reduced value, which was 73% ( P < 0.01) of the control level, 1 day after exposure to 10 ppm NO 2. Subsequently, the activity increased to 1.14-fold that of the control during exposure to 10 (at the fifth day) and 4 ppm (at the fourth day) NO 2. Components of microsomal electron-transport systems also showed a slightly elevated value during exposure to 4 ppm NO 2. Seven days after exposure, the cytochrome P-450 content was decreased to 61% ( P < 0.01) of the control level, while other components were retained at control levels. A significant reduction in the cytochrome P-450 content was also observed at the exposure concentration of 1.2 ppm, but not of 0.4 ppm, at the seventh day.

The influence of linoleic acid intake on electron transport system components

AbstractGroups of young rats were fed a basal diet with beef tallow (BT) or corn oil (CO) added to provide 4 or 19% energy as linoleic acid. Mitochondria isolated from the livers of the rats fed the CO contained a significantly lower concentration of b‐type cytochrome and significantly higher concentrations of cytochromes c, c1 and aa3. Cytochrome c oxidase activity also was elevated. The spectral characteristics of the b‐type cytochrome varied between the 2 groups. The mitochondria from the rats fed CO contained relatively more of the cytochrome b‐558 component whereas mitochondria from the BT group contained more of the cytochrome b‐562 component. The classical antimycin A inhibition of electron transport between cytochromes b and c1 was partially bypassed in mitochondria with the more fluid membrane. The activation energy for cytochrome c oxidase in mitochondria from this group was significantly higher. These differences may be traced to the physical characteristics of the inner mitochondrial membrane.