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1.
Zorov DB Bannikova SY Belousov VV Vyssokikh MY Zorova LD Isaev NK Krasnikov BF Plotnikov EY 《Biochemistry. Biokhimii?a》2005,70(2):215-221
Chemical and physiological functions of molecular oxygen and reactive oxygen species (ROS)and existing equilibrium between pools of pro-oxidants and anti-oxidants providing steady state ROS level vital for normal mitochondrial and cell functioning are reviewed. The presence of intracellular oxygen and ROS sensors is postulated and few candidates for this role are suggested. Possible involvement of ROS in the process of fragmentation of mitochondrial reticulum made of long mitochondrial filaments serving in the cell as electric cables, as well as the role of ROS in apoptosis and programmed mitochondrial destruction (mitoptosis) are reviewed. The critical role of ROS in destructive processes under ischemia/reoxygenation and ischemic preconditioning is discussed. Mitochondrial permeability transition gets special consideration as a possible component of the apoptotic cascade, resulting in excessive ROS induced ROS release.Translated from Biokhimiya, Vol. 70, No. 2, 2005, pp. 265–272.Original Russian Text Copyright ¢ 2005 by Zorov, Bannikova, Belousov, Vyssokikh, Zorova, Isaev, Krasnikov, Plotnikov.This revised version was published online in April 2005 with corrections to the post codes. 相似文献
2.
Simonian RA Pustovidko AV Vyssokikh MIu Skulachev VP 《Biochemistry. Biokhimii?a》2006,71(12):1365-1369
The mechanism of uncoupling by lauryl sulfate (LS) has been studied. The very fact that uncoupling by low concentration of LS (a strong acid) resembles very much that by fatty acids (weak acids) was used as an argument against the fatty acid cycling scheme of uncoupling where protonated fatty acids operate as a protonophore. We have found that rat liver and heart muscle mitochondria can be uncoupled by low (70 microM) LS concentration in a fashion completely arrested by the ATP/ADP antiporter inhibitor carboxyatractylate (CAtr). On the other hand, uncoupling by two-fold higher LS concentration is not sensitive to CAtr. Addition of oleate desensitizes mitochondria to low LS so that addition of bovine serum albumin becomes necessary to recouple mitochondria. The data are accounted for assuming that low LS releases endogenous fatty acids from some mitochondrial depots, and these fatty acids are responsible for uncoupling. As to high LS, it causes a nonspecific (CAtr-insensitive) damage to the mitochondrial membrane. 相似文献
3.
Severina II Vyssokikh MY Pustovidko AV Simonyan RA Rokitskaya TI Skulachev VP 《Biochimica et biophysica acta》2007,1767(9):1164-1168
In this paper, we studied effects of phosphonium dications P2C5 and P2C10 on bilayer planar phospholipid membrane (BLM) and rat liver mitochondria. In line with our previous observations [M.F. Ross, T. Da Ros, F.H. Blaikie, T.A. Prime, C.M. Porteous, I.I. Severina, V.P. Skulachev, H.G. Kjaergaard, R.A. Smith, M.P. Murphy, Accumulation of lipophilic dications by mitochondria and cells, Biochem. J. 400 (2006) 199-208], we showed both P2C5 and P2C10 are cationic penetrants for BLM. They generated transmembrane diffusion potential (Delta Psi), the compartment with a lower dication concentration positive. However, the Delta Psi values measured proved to be lower that the Nernstian. This fact could be explained by rather low BLM conductance for the cations at their small concentrations and by induction of some BLM damage at their large concentrations. The damage in question consisted in appearance of non-Ohmic current/voltage relationships which increased in time. Such a non-Ohmicity was especially strong at Delta Psi >100 mV. Addition of penetrating lipophilic anion TPB, which increases the BLM conductance for lipophilic cations, yielded the Nernstian Delta Psi, i.e. 30 mV per ten-fold dication gradient. In the State 4 mitochondria, dications stimulated respiration and lowered Delta Psi. Moreover, they inhibited the State 3 respiration with succinate or glutamate and malate (but not with TMPD and ascorbate) in an uncoupler-sensitive fashion. Effect on the in State 4 mitochondria, similarly to that on BLM, was accounted for by a time-dependent membrane damage. On the other hand, the State 3 effect was most probably due to inhibition of the respiratory chain Complex I and/or Complex III. The damaging and inhibitory activities of lipophilic dications should be taken into account when one considers a possibility to use them as a vehicle to target antioxidants or other compounds to mitochondria. 相似文献
4.
Vyssokikh MY Goncharova NY Zhuravlyova AV Zorova LD Kirichenko VV Krasnikov BF Kuzminova AE Melikov KC Melik-Nubarov NS Samsonov AV Belousov VV Prischepova AE Zorov DB 《Biochemistry. Biokhimii?a》1999,64(4):390-398
A Triton X-100 extract from rat brain mitochondria was obtained using low detergent/protein ratio. From this extract a proteinaceous complex was purified; its molecular weight was as high as 880 kD. The complex contained both hexokinase and creatine kinase activity. When incorporated into phospholipid bilayer membranes, the complex formed a channel whose activity was different than the channel activity of purified porin isolated either by adsorption chromatography or by dissociation from protein complexes. A ligand of the mitochondrial benzodiazepine receptor (Ro5-4864) in submicromolar concentrations had an apparent influence on the kinetic behavior of enzymatic coupling of hexokinase and creatine kinase. It is suggested that the 880-kD complex is formed by mitochondrial contact sites. The role of the isolated protein complex in the formation of nonspecific permeability in mitochondria is discussed. 相似文献
5.
Vyssokikh MY Zorova L Zorov D Heimlich G Jürgensmeier JJ Brdiczka D 《Molecular biology reports》2002,29(1-2):93-96
The mechanism by which external Bax releases cytochrome c is still controversial and may also depend on the type of mitochondria and the actual localisation of cytochrome c. Outer membrane porin acquires high binding affinity for hexokinase by interacting with the adenine nucleotide translocator (ANT) in the contact sites. (I) The hexokinase protein was thus used as a tool to isolate the contact site forming complex between outer membrane porin and inner membrane ANT from a TritonX100 extract of brain membranes. (II) A significant amount of cytochrome c was co-purified with the isolated hexokinase porin ANT complexes that were reconstituted in phospholipid vesicles. Bax-C released the endogenous cytochrome c from the vesicles without forming unspecific pores. This was shown by loading the vesicles with malate that was not liberated by Bax-C. (III) The Bax-C effect was dependent on a specific association of cytochrome c with the porin ANT complex, as dissociation of the complex by bongkrekate abolished the Bax dependent cytochrome c liberation. (IV) The Bax-C effect was as well suppressed by hexokinase phosphorylating glucose. 相似文献
6.
Y. N. Antonenko A. V. Avetisyan L. E. Bakeeva B. V. Chernyak V. A. Chertkov L. V. Domnina O. Yu. Ivanova D. S. Izyumov L. S. Khailova S. S. Klishin G. A. Korshunova K. G. Lyamzaev M. S. Muntyan O. K. Nepryakhina A. A. Pashkovskaya O. Yu. Pletjushkina A. V. Pustovidko V. A. Roginsky T. I. Rokitskaya E. K. Ruuge V. B. Saprunova I. I. Severina R. A. Simonyan I. V. Skulachev M. V. Skulachev N. V. Sumbatyan I. V. Sviryaeva V. N. Tashlitsky J. M. Vassiliev M. Yu. Vyssokikh L. S. Yaguzhinsky A. A. Zamyatnin Jr. V. P. Skulachev 《Biochemistry. Biokhimii?a》2008,73(12):1273-1287
Synthesis of cationic plastoquinone derivatives (SkQs) containing positively charged phosphonium or rhodamine moieties connected
to plastoquinone by decane or pentane linkers is described. It is shown that SkQs (i) easily penetrate through planar, mitochondrial,
and outer cell membranes, (ii) at low (nanomolar) concentrations, posses strong antioxidant activity in aqueous solution,
BLM, lipid micelles, liposomes, isolated mitochondria, and cells, (iii) at higher (micromolar) concentrations, show pronounced
prooxidant activity, the “window” between anti- and prooxidant concentrations being very much larger than for MitoQ, a cationic
ubiquinone derivative showing very much lower antioxidant activity and higher prooxidant activity, (iv) are reduced by the
respiratory chain to SkQH2, the rate of oxidation of SkQH2 being lower than the rate of SkQ reduction, and (v) prevent oxidation of mitochondrial cardiolipin by OH·. In HeLa cells and human fibroblasts, SkQs operate as powerful inhibitors of the ROS-induced apoptosis and necrosis. For
the two most active SkQs, namely SkQ1 and SkQR1, C
1/2 values for inhibition of the H2O2-induced apoptosis in fibroblasts appear to be as low as 1·10−11 and 8·10−13 M, respectively. SkQR1, a fluorescent representative of the SkQ family, specifically stains a single type of organelles in
the living cell, i.e. energized mitochondria. Such specificity is explained by the fact that it is the mitochondrial matrix
that is the only negatively-charged compartment inside the cell. Assuming that the Δψ values on the outer cell and inner mitochondrial
membranes are about 60 and 180 mV, respectively, and taking into account distribution coefficient of SkQ1 between lipid and
water (about 13,000: 1), the SkQ1 concentration in the inner leaflet of the inner mitochondrial membrane should be 1.3·108 times higher than in the extracellular space. This explains the very high efficiency of such compounds in experiments on
cell cultures. It is concluded that SkQs are rechargeable, mitochondria-targeted antioxidants of very high efficiency and
specificity. Therefore, they might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner
mitochondrial membrane in vivo.
Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.
Published in Russian in Biokhimiya, 2008, Vol. 73, No. 12, pp. 1589–1606.
This and the following four articles were written by the request of the Editorial Board of Biochemistry (Moscow). 相似文献
7.
Hydrogen peroxide produced inside mitochondria takes part in cell-to-cell transmission of apoptotic signal 总被引:2,自引:0,他引:2
Pletjushkina OY Fetisova EK Lyamzaev KG Ivanova OY Domnina LV Vyssokikh MY Pustovidko AV Alexeevski AV Alexeevski DA Vasiliev JM Murphy MP Chernyak BV Skulachev VP 《Biochemistry. Biokhimii?a》2006,71(1):60-67
In monolayer of HeLa cells treated with tumor necrosis factor (TNF), apoptotic cells formed clusters indicating possible transmission of apoptotic signal via the culture media. To investigate this phenomenon, a simple method of enabling two cell cultures to interact has been employed. Two coverslips were placed side by side in a Petri dish, one coverslip covered with apoptogen-treated cells (the inducer) and another with non-treated cells (the recipient). TNF, staurosporine, or H2O2 treatment of the inducer cells is shown to initiate apoptosis on the recipient coverslip. This effect is increased by a catalase inhibitor aminotriazole and is arrested by addition of catalase or by pre-treatment of either the inducer or the recipient cells with nanomolar concentrations of mitochondria-targeted cationic antioxidant MitoQ (10-(6 -ubiquinolyl)decyltriphenylphosphonium), which specifically arrests H2O2-induced apoptosis. The action of MitoQ is abolished by an uncoupler preventing accumulation of MitoQ in mitochondria. It is concluded that reactive oxygen species (ROS) produced by mitochondria in the apoptotic cells initiate the release of H2O2 from these cells. The H2O2 released is employed as a long-distance cell suicide messenger. In processing of such a signal by the recipient cells, mitochondrial ROS production is also involved. It is suggested that the described phenomenon may be involved in expansion of the apoptotic region around a damaged part of the tissue during heart attack or stroke as well as in "organoptosis", i.e. disappearance of organs during ontogenesis. 相似文献
8.
Mitochondrial porin was identified in Rickettsia prowazekii by Western blot analysis of whole cells and membrane fractions with monoclonal antibody against porin VDAC 1 of animal mitochondria. Using the BLAST server, no protein sequences homologous to mitochondrial porin were found among the rickettsial genomes. Rickettsiae also do not contain their own porin. The protein imported by rickettsiae is weakly extracted by nonionic detergents and, like porin in mitochondria, is insensitive to proteinase K in whole cells. Immunocytochemical analysis showed that it localizes to the outer membrane of the bacterial cells. These data support an earlier suggestion about import by rickettsiae of indispensable proteins from cytoplasm of the host cell as a molecular basis of obligate intracellular parasitism. They are also consistent with the hypothesis invoking a transfer of genes specifying surface proteins from the last common ancestor of rickettsiae and mitochondria to the host genome, and preservation by rickettsiae of the primitive ability to import these proteins. 相似文献
9.
V. I. Kargin K. A. Motovilov M. Yu. Vyssokikh L. S. Yaguzhinsky 《Biochemistry (Moscow) Supplemental Series A: Membrane and Cell Biology》2008,2(1):33-39
Effects of the coenzyme Q analog (MitoQ10) carrying a positively charged decyltetraphenylphosphonium group on functional activity of phosphorylating liver mitochondria were studied. Using inhibitory analysis it was found that at micromolar concentrations this quinone is reduced by NADH-dependent DT-diaphorase. Under conditions of malate oxidation, MitoQ10 stimulates electron transfer from NADH to oxygen by shunting the block of rotenone-induced electron transport in Complex I. Steady-state mitochondrial respiration induced by rotenone and MitoQ10 (1 μM), as well as K3 shunt are both blocked by the DT-diaphorase inhibitor dicumarol, the Complex III inhibitor myxothiazole, and the cytochrome oxidase inhibitor cyanide. The electron transport chain induced in liver mitochondria by MitoQ10 in the presence of rotenone appears as follows: NADH → DT-diaphorase → MitoQ10 → Complex III → Complex IV → O2. Under conditions of malate (but not succinate) oxidation, MitoQ10 and high concentrations of vitamin K3 induce in mitochondria cyanide-resistant respiration and opening of the nonspecific pore eventually resulting in inhibition of oxidative phosphorylation. It is concluded that MitoQ10 should be regarded as an analog of hydrophilic quinones (vitamin K3, duroquinone, etc.) widely known as substrates for mitochondrial DT-diaphorase not interacting with CoQ10 rather than as a natural CoQ10 analog. 相似文献
10.
S. M. Ojovan L. E. Bakeeva O. V. Shtaer O. V. Kamzolkina M. Yu. Vyssokikh 《Biochemistry (Moscow) Supplemental Series A: Membrane and Cell Biology》2010,4(1):38-42
A beneficial effect of mitochondria targeted antioxidant (MTA) SkQ1 added to the culture medium on life span of Podospora anserina was revealed. As was shown earlier, optimal concentration was 400 nM. SkQ1 was shown to increase P. anserina life span 2.4 times, at the same time maintaining native cell ultrastructure: degradative alterations were not revealed.
Significant reorganization of P. anserina cell ultrastructure was detected. These changes were not described earlier. The greatest structural changes proceeded in
mitochondria. Specific character of these alterations suggests an essential role of oxidative stress in senescence of P. anserina. 相似文献