Involvement of Reactive Oxygen Species in Plant Mitochondrial Response to Low-Temperature Stress

The review presents data for the generation of the reactive oxygen species (ROS) in mitochondria during low-temperature stress. The relation of lipid peroxidation processes in membranes to the induction of low-temperature stress is demonstrated. The data for the involvement of the mitochondrial uncoupling proteins and the processes of uncoupling oxidation and phosphorylation in the regulation of mitochondrial ROS formation during low-temperature stress are considered.     

Effect of Melafen on functional efficiency of mitochondrial membranes from sugar beet taproots

Mitochondria were isolated from sugar beet (Beta vulgaris L) taproots and incubated in the presence of low concentrations of Melafen (2 × 10^?9 and 4 × 10^?12 M). This treatment of mitochondrial membranes induced an appreciable decrease in microviscosity of superficial lipids in the lipid bilayer and a parallel increase in microviscosity of the deeply immersed lipid regions adjacent to membrane proteins. Melafen had no effect on fluorescence of lipid peroxidation products in membranes of freshly prepared mitochondria but declined this fluorescence to control values in artificially aged mitochondria. Melafen raised the maximum rates for oxidation of NAD-dependent substrates, elevated the efficiency of oxidative phosphorylation, and activated electron transport in the terminal (cytochrome oxidase) step of mitochondrial respiratory chain, which implies the activation of energy metabolism within the cell. The acceleration of electron transport through the terminal step of mitochondrial respiratory chain was apparently accompanied by retardation of lipid peroxidation, which prevented impairment of mitochondrial membranes under stress conditions. A proposal is put forward that some properties of Melafen are favorable for adaptogenesis because its effects on mitochondrial energy metabolism depended on the functional state of mitochondria.     

Effect of succinate on mitochondrial lipid peroxidation. 2. The protective effect of succinate against functional and structural changes induced by lipid peroxidation

The damaging effects of ADP/Fe/NADPH-induced lipid peroxidation were studied on the enzymes and membranes of rat liver mitochondria. Succinate, an inhibitor of mitochondrial lipid peroxidation, prevented or delayed most of the damage caused by the peroxidation on different mitochondrial structures and functions. There were marked abnormalities on the electrophoretic pattern of mitochondrial proteins during the course of lipid peroxidation. The disappearance of particular polypeptide bands and the accumulation of high-molecular-weight aggregates could be observed. Succinate was found to delay these effects. As a consequence of lipid peroxidation the succinate oxidase activity of mitochondria was decreased. The succinate dehydrogenase enzyme and the component(s) of the respiratory chain were inactivated. Succinate prevented the inactivation of succinate dehydrogenase but did not protect the other components of terminal oxidation chain. From the matrix enzymes the glutamate dehydrogenase retained its full activity but the NADP-linked isocitrate dehydrogenase was inactivated. The mitochondrial membranes became permeable to large protein molecules. Succinate prevented the inactivation of isocitrate dehydrogenase and delayed the release of protein molecules from mitochondria.     

Possible participation of a free-radical lipid intermediate in the coupling of oxidation and phosphorylation

Data shown propose two regimes of lipid radicals and oxygen utilization realized in mitochondrial membranes. The first one--lipid peroxidation, i.e. interaction of lipid radical and oxygen is an empty step. In switching this regime to the functional one lipid peroxidation is inhibited. Setting L. -dependent coupling apparatus on phosphorylation in mitochondria takes place in the presence of ADP and Pi.     

The role of lipid radicals in electron transport and energy transformation

Data given propose two regimes of lipid radicals and oxygen utilization realized in microsomal and mitochondrial membranes. The first one, lipid peroxidation, i.e. interaction of lipid radicals and oxygen is an empty step. In converting this regime to the functional one NADPH-dependent lipid peroxidation is inhibited. A change of this regime to the functional one in microsome demand the presence of hydroxylation substrates. Setting lipid radical-dependent coupling apparatus on phosphorylation in mitochondria occur in the presence of ADP and Pi-phosphorylation substrates.     

The cold but not hard fats in ectotherms: consequences of lipid restructuring on susceptibility of biological membranes to peroxidation,a review

The production of reactive oxygen species is a regular feature of life in the presence of oxygen. Some reactive oxygen species possess sufficient energy to initiate lipid peroxidation in biological membranes, self-propagating reactions with the potential to damage membranes by altering their physical properties and ultimately their function. Two of the most prominent patterns of lipid restructuring in membranes of ectotherms involve contents of polyunsaturated fatty acids and ratios of the abundant phospholipids, phosphatidylcholine and phosphatidylethanolamine. Since polyunsaturated fatty acids and phosphatidylethanolamine are particularly vulnerable to oxidation, it is likely that higher contents of these lipids at low body temperature elevate the inherent susceptibility of membranes to lipid peroxidation. Although membranes from animals living at low body temperatures may be more prone to oxidation, the generation of reactive oxygen species and lipid peroxidation are sensitive to temperature. These scenarios raise the possibility that membrane susceptibility to lipid peroxidation is conserved at physiological temperatures. Reduced levels of polyunsaturated fatty acids and phosphatidylethanolamine may protect membranes at warm temperatures from deleterious oxidations when rates of reactive oxygen species production and lipid peroxidation are relatively high. At low temperatures, enhanced susceptibility may ensure sufficient lipid peroxidation for cellular processes that require lipid oxidation products.     

Characteristics and relationship of mitochondrial and microsomal oxidation processes with various intensities of lipid peroxidation]

Mitochondrial and microsomal oxidation reactions were studied at varying intensities of lipid peroxidation (LPO). The latter were modelled by using thermal burn and combined radiation-thermal injury in animals. It was found that the differences in the intensity and duration of free radical oxidation and LPO reactions may lead to the activation or inhibition of mitochondrial respiration due to the oxidative phosphorylation uncoupling and impaired microsomal and microsomal-mitochondrial intermembrane electron transport and depend on the activities of superoxide dismutase, glutathione reductase and catalase.     

Protective role of pinacidil against adrenaline-induced myocardium injury in guinea pig liver mitochondria

We investigated the role of the ATP-sensitive potassium channel opener pinacidil and blocker glibenclamide on guinea pig liver mitochondrial function, and a possible significance of pinacidil in the pharmacological treatment during myocardium dystrophy. First, a series of experiments was performed to determine the effect of pinacidil and glibenclamide on mitochondrial oxygen consumption. We found that pinacidil increased the rate of mitochondrial respiration for FAD-generated substrate (succinate oxidation), but was most effective for α-ketoglutarate oxidation with enhancement of respiratory control ratio. Oxidation of FAD-generated substrate inhibited efficiency of phosphorylation for α-ketoglutarate oxidation in pinacidil-treated animals. Glibenclamide decreased the rate of respiration with the lowest value of efficiency of phosphorylation, especially for α-ketoglutarate oxidation. A second series of experiments was performed to determine the effects of pinacidil and glibenclamide on oxidative phosphorylation during adrenaline-induced myocardium dystrophy. The increase in respiratory control ratio and efficiency of phosphorylation for α-ketoglutarate oxidation was greater than for succinate oxidation in mitochondria of pinacidil-pretreated animals during myocardium dystrophy. Inhibitory analysis with malonate suggested that endogenous succinate increased oxidation of NADH-generated substrates in mitochondria. Pinacidil is mainly involved in the adrenaline-induced alterations of mitochondrial function due to elevation of phosphorylation efficiency for α-ketoglutarate oxidation and a decreased level of lipid peroxidation.     

Olive oil supplemented with vitamin E affects mitochondrial coenzyme Q levels in liver of rats after an oxidative stress induced by adriamycin.

In this study we have evaluated the supplementation of olive oil with vitamin E on coenzyme Q concentration and lipid peroxidation in rat liver mitochondrial membranes. Four groups of rats were fed on virgin olive, olive plus 200 mg/kg of vitamin E or sunflower oils as lipid dietary source. To provoke an oxidative stress rats were administered intraperitoneally 10 mg/kg/day of adriamycin the last two days of the experiment. Animals fed on olive oil plus vitamin E had significantly higher coenzyme Q and vitamin E levels but a lower mitochondrial hydroperoxide concentration than rats fed on olive oil. Retinol levels were not affected, by either different diets or adriamycin treatment. In conclusion, an increase in coenzyme Q and alpha-tocopherol in these membranes can be a basis for protection against oxidation and improvement in antioxidant capacity.     

The role of membrane structure in activation of mitochondrial phospholipases. 2. Mechanism of crambin action on the activities of mitochondrial membrane phospholipases and microviscosity

Effects of crambin on the phospholipase activity, lipid peroxidation and structure of mitochondrial membranes have been investigated. Crambin has been shown to inhibit lipid peroxidation and phospholipase activity induced by Ca2+ and freezing-thawing of mitochondria. As shown by ESR studies, these effects are based on the ability of crambin to cause changes in mitochondrial membrane structure.     

Lipidg Peroxidation in Liver and Ehrlich Ascites Cell Mitochondria

Ehrlich ascites cell mitochondria are highly resistant to lipid peroxidation as compared to liver mitochondria from host animals. Succinate protects mitochondria from peroxidative damage, proteins from crosslinks, enzymes from inactivation of the enzymes and membranes from permeability changes. The sensitivity of Ehrlich ascites cell mitochondrial membranes to lipid peroxidation is significantly increased in sub-mitochondrial particles. Lipid peroxidation in tumour mitochondrial membranes can not be diminished by succinate as effectively as in liver mitochondria. Ascites cell mitochondria seems to be protected very efficiently from peroxidative damage by a glutathione-dependent mechanism.     

Mitochondrial lipid peroxidation is influenced by dietary factors in early colon carcinogenesis

Oxidative damage to mitochondrial proteins, lipids, and DNA seem to influence the promotion and progression of tumors. High-fat diets and diets high in iron decrease manganese superoxide dismutase activity, a mitochondrial antioxidant, in colon mucosa. Lipid peroxidation products are low in microsomal preparations from colonic mucosa even under peroxide-inducing conditions. However, damage specific to mitochondrial membranes is unknown. This study was designed to investigate dietary lipid and iron effects on fatty acid incorporation and lipid peroxide formation in mitochondrial membranes of colonic mucosa. Male Fischer rats were fed high-fat diets containing either corn oil or menhaden oil with an iron level of either 35 or 535 mg/kg diet. Animals were given two injections of the colon carcinogen, azoxymethane, or saline. Colon tissue was collected 1 and 6 weeks after injections. Mitochondrial and microsomal fractions were prepared for fatty acid analysis and quantitation of lipid peroxidation products. Results showed that lipid composition of both subcellular fractions were influenced by diet. Fatty acid composition of mitochondria differed from microsomes, but overall saturation remained constant. Peroxidation products in mitochondrial membranes were significantly greater than in microsomal membranes. Dietary treatment significantly affected mitochondrial peroxidation in carcinogen-treated animals. Therefore, mitochondria from colon mucosa are more susceptible to peroxidation than are microsomes, dietary factors influence the degree of peroxidation, and the resulting damage may be important in early colon carcinogenesis.     

Myoglobin causes oxidative stress,increase of NO production and dysfunction of kidney's mitochondria

Rhabdomyolysis or crush syndrome is a pathology caused by muscle injury resulting in acute renal failure. The latest data give strong evidence that this syndrome caused by accumulation of muscle breakdown products in the blood stream is associated with oxidative stress with primary role of mitochondria. In order to evaluate the significance of oxidative stress under rhabdomyolysis we explored the direct effect of myoglobin on renal tubules and isolated kidney mitochondria while measuring mitochondrial respiratory control, production of reactive oxygen and nitrogen species and lipid peroxidation. In parallel, we evaluated mitochondrial damage under myoglobinurea in vivo. An increase of lipid peroxidation products in kidney mitochondria and release of cytochrome c was detected on the first day of myoglobinuria. In mitochondria incubated with myoglobin we detected respiratory control drop, uncoupling of oxidative phosphorylation, an increase of lipid peroxidation products and stimulated NO synthesis. Mitochondrial pore inhibitor, cyclosporine A, mitochondria-targeted antioxidant (SkQ1) and deferoxamine (Fe-chelator and ferryl-myoglobin reducer) abrogated these events. Similar effects (oxidative stress and mitochondrial dysfunction) were revealed when myoglobin was added to isolated renal tubules. Thus, rhabdomyolysis can be considered as oxidative stress-mediated pathology with mitochondria to be the primary target and possibly the source of reactive oxygen and nitrogen species. We speculate that rhabdomyolysis-induced kidney damage involves direct interaction of myoglobin with mitochondria possibly resulting in iron ions release from myoglobin's heme, which promotes the peroxidation of mitochondrial membranes. Usage of mitochondrial permeability transition blockers, Fe-chelators or mitochondria-targeted antioxidants, may bring salvage from this pathology.     

Induction of lipid peroxidation in the erythrocytes during cholesterol oxidation catalysed by cholesterol oxidase

Using the chemiluminescence technique to assay the activity of cholesterol oxidase it has been shown that enzymic oxidation of cholesterol to cholest-4-en-3-one red cell membranes is accompanied by accumulation of lipid peroxidation products--malonyl dialdehyde (MDA). The amount of MDA formed was dependent on the amount of cholesterol oxidized. The free radical scavenger 4-methyl-2,6-ditretbutylphenol, the transition metal chelator EDTA and catalase inhibited lipid peroxidation in red blood cells. The participation of OH radicals in the initiation of lipid peroxidation in red cell membranes in the course of cholesterol oxidation is discussed.     

Prooxidant and antioxidant effects of ascorbate on tBuOOH-induced erythrocyte membrane damage

1. t-Butylhydroperoxide (tBuOOH) a lipoperoxide analog, causes rapid and considerable sulphydryl (SH) oxidation but almost no lipid peroxidation in red blood cell membranes (ghosts) containing no detectable haemoglobin. 2. tBuOOH, in the presence of ascorbate, produces significant lipid peroxidation the level of which is proportional to the ascorbate concentration. The initiation of lipid peroxidation is thought to occur by the reactive tBuO (butoxyl) species via the reductive decomposition of tBuOOH by ascorbate. 3. Ascorbate protects ghost membranes from the tBuOOH-induced SH oxidation in a dose-dependent fashion. 4. There is no parallelism between lipid peroxidation and SH oxidation in these systems. This suggests that the two processes occur independently of each other. 5. These findings indicate that, simultaneously, ascorbate can have both a protective and a prooxidant action in different membrane components under the same oxidative stress.     

Cholesterol and peroxidized cardiolipin in mitochondrial membrane properties,permeabilization and cell death

Mitochondria are known to actively regulate cell death with the final phenotype of demise being determined by the metabolic and energetic status of the cell. Mitochondrial membrane permeabilization (MMP) is a critical event in cell death, as it regulates the degree of mitochondrial dysfunction and the release of intermembrane proteins that function in the activation and assembly of caspases. In addition to the crucial role of proapoptotic members of the Bcl-2 family, the lipid composition of the mitochondrial membranes is increasingly recognized to modulate MMP and hence cell death. The unphysiological accumulation of cholesterol in mitochondrial membranes regulates their physical properties, facilitating or impairing MMP during Bax and death ligand-induced cell death depending on the level of mitochondrial GSH (mGSH), which in turn regulates the oxidation status of cardiolipin. Cholesterol-mediated mGSH depletion stimulates TNF-induced reactive oxygen species and subsequent cardiolipin peroxidation, which destabilizes the lipid bilayer and potentiates Bax-induced membrane permeabilization. These data suggest that the balance of mitochondrial cholesterol to peroxidized cardiolipin regulates mitochondrial membrane properties and permeabilization, emerging as a rheostat in cell death.     

Inhibition of phospholipid hydrolysis by phospholipase A2 in microsomal and mitochondrial membranes subjected to lipid peroxidation

The rate of phospholipid hydrolysis in rat liver microsomal and mitochondrial membranes catalyzed by phospholipase A2 was shown to decrease after ascorbate + Fe2+-induced lipid peroxidation. The degree of inhibition was linearly dependent on the amount of lipid peroxidation products (malonyl dialdehyde) accumulated in the membrane. The decreased phospholipid hydrolysis rate in membranes after lipid peroxidation was registered using phospholipases A2 from two sources: porcine pancreas and bee venom. It was established that the inhibitory action of phospholipid peroxidation products was not linked with a direct effect on the enzyme and was not caused by depletion of phospholipase reaction substrates (as a result of lipid peroxidation). A possible role of lateral separation of oxidized and non-oxidized lipid phases in the mechanisms of inhibition of phospholipid hydrolysis by phospholipase A2 is discussed.     

Effect of a zinc-deficient diet on lipid peroxidation in liver and tumor subcellular membranes

The effect of a zinc-deficient diet on lipid peroxidation in liver and tumor mitochondrial and microsomal membrane preparations from BALB/c mice was investigated. Mitochondrial and microsomal membranes from both tissues displayed increased rates of in vitro peroxidation, both enzymatic and nonenzymatic. Measurement of in vivo peroxidation, using diene conjugation as an index of measurement revealed slight increases in tissues from zinc-deficient animals that were not statistically significant. Serum lipoperoxides analyzed from all three groups revealed no significant differences. The results point to an alteration in the peroxidation potential of mitochondrial and microsomal membranes due to zinc deficiency which may be related to an alteration in fatty acid composition.     

Lipid peroxidation in membranes and low-density lipoproteins: similarities and differences

Lipid peroxidation has been a central aspect of studies of the nature of free radical species and their origin in biological systems. Moreover, there has been a growing interest in lipid peroxidation based on evidence that biologically active products are formed that influence cell function and the course of major human diseases. A review of the work in this area is contributed by Lars Ernster is presented with an emphasis on the mechanisms by which lipid peroxidation is initiated in biological lipid systems. Based on what was described for metal catalyzed oxidation of cell membranes, and the seminal studies on cytochrome P-450-mediated lipid peroxidation, several parallel and distinct aspects of lipid peroxidation are described. A key distinction between lipid peroxidation in cell membranes and lipoproteins reveals aspects of free radical initiated reactions involving proteins and lipids that determine pro- vs. anti-oxidant outcomes, and the role of lipid structure and order in delineating the progress of oxidation.     

Change in the structure of rat liver mitochondrial membranes under the effect of ionizing radiation

The effect of gamma-irradiation (under 0-10(3) Gy) on the intensity of lipid peroxidation, the microviscosity of annular and free lipids and the polarization of membrane proteins tryptophan fluorescence was studied in the outer and inner mitochondrial membranes. Some specific individual peculiarities of the mitochondrial membranes post-radiation changes were established.