György Báthori - Academia.edu (original) (raw)
Papers by György Báthori
Biochimica Et Biophysica Acta-biomembranes, 1993
The pore-forming protein porin has been isolated from rat heart mitochondria and reconstituted in... more The pore-forming protein porin has been isolated from rat heart mitochondria and reconstituted in phospholipid vesicles of different composition. Rapid release of anions, cations and non-charged molecules has been demonstrated from the proteoliposomes but not from the protein-free liposomes. In spite of its higher molecular mass and charges, the movement of ATP was almost as fast as that of inorganic phosphate. Polyanion (1:2:3 copolymer of methacrylate/maleate/styrene), a potent inhibitor of porin residing in the mitochondrial contact sites decreased the solute movements but did not completely block any of the investigated transport processes (phosphate, chloride, ATP). Alterations of the lipid environment had significant effect: an increase in the proportion of soybean phospholipids to egg yolk phospholipids resulted in a decrease in the amount of transported substance but did not fully inhibit the ion movements. It is concluded that the transport properties of porin reconstituted in artificial phospholipid membranes are different from the characteristics of porin prevailing in the mitochondrial contact sites and additional regulatory factors are suggested to be effective in the intact mitochondria.
Biochimica Et Biophysica Acta-biomembranes, 1995
Transport properties of mitochondrial porin were investigated on the basis of changes in the acti... more Transport properties of mitochondrial porin were investigated on the basis of changes in the activity of hexokinase utilizing external ATP. Production of glucose: 6-phosphate is inhibited by polyanion both in intact brain mitochondria and in contact point vesicles. Hexokinase activity is restored by solubilization of the enzyme by high ionic strength or 0.5-1% Triton X-100. In very low concentrations (0.001–0.005%) Triton does not mobilize hexokinase from its binding sites but it is able to release polyanion-inhibition completely. This finding provides an explanation for the discrepancy observed in the transport properties of porin when studied ‘in situ’ or in artificial lipid membranes.
Critical Reviews in Therapeutic Drug Carrier Systems, 2004
Caveolae are bottleshape-like invaginations of the plasma membrane. After internalization they ar... more Caveolae are bottleshape-like invaginations of the plasma membrane. After internalization they are involved in endocytosis, transcytosis, potocytosis, and pinocytosis. Our recently expanded knowledge has made clear that various molecules and macromolecular complexes enter the cells after docking on caveolar receptors, before subsequent internalization of the caveolae. The internalization is initiated by the ligand receptor interaction. Folate, cholesterol, serum lipoproteins, and liposomes are among the most common examples. It is important to point out that, in contrast to the classic clathrin-dependent endocytosis, the caveolar internalization pathway seems to avoid the lysosomes. Internalized caveolae fuse with caveosomes, and the caveosomes deliver their contents into other subcellular (non-lysosomal) compartments. The bypass of the acidic and harmful milieu might be a major advantage for drug delivery via the caveolar pathway. Not all cell types have caveolae. Cells, where the Caveolin I protein is not expressed, do not develop caveolar invaginations. However, these cells have caveolar-equivalent plasma membrane domains, so-called "lipid rafts." Lipid rafts are assembled from the same lipid constituents and proteins as caveolae, but they are flat. Specific ligands may also dock on appropriate receptors of the raft domain. As a complication, certain types of ligand-covered raft receptors can migrate to clathrin-coated pits and get internalized via clathrin-coated vesicles. Nevertheless, suitable ligands or antibodies developed against proteins of the caveolar/raft domains may selectively direct the attached drug carrier to the less harmful caveolar/raft pathway. Thus, understanding of caveolar transport may help in the rational design of more effective drug carriers.
Journal of Bioenergetics and Biomembranes, 1996
The high-conductance channels present in the outer membranes of wild-type and porin-less yeast mi... more The high-conductance channels present in the outer membranes of wild-type and porin-less yeast mitochondria have been characterized electrophysiologically after incorporation in planar bilayer membranes. The most prominent activity was ascribed to a voltage-dependent, substaterich, cationic channel which generally inactivated at potentials positive in thecis compartment, in agreement with the observations from patch-clamp experiments on porin-less mitoplasts. This channel has been identified as the so-called “peptide-sensitive channel” (PSC). We also observed similar channels displaying either no inactivation, or inactivation at both positive and negative potentials. These latter properties match those already described for mammalian and yeast PSC, respectively. These different behaviors are tentatively explained as arising from the presence, or lack of, peptides bound to the PSC. Very high conductances, apparently due to cooperative gating, were frequently displayed. In wild-type membranes, activity ascribable to the porin was also observed.
Biochimica Et Biophysica Acta-biomembranes, 1995
Patch-clamp and planar bilayer experiments on porin-less yeast mitochondria have allowed the char... more Patch-clamp and planar bilayer experiments on porin-less yeast mitochondria have allowed the characterization of a cationic channel activated at matrix-side positive (unphysiological) potentials. In voltage-pulse experiments, inactivation was a faster process than activation and the time constant for inactivation was more steeply dependent on voltage than the one for activation. The channel exhibited various conductance states whose occupancy depended on the applied transmembrane potential. In bilayer experiments, the presence of the pCOx-IV leader peptide induced fast gating in a voltage-dependent manner. A comparison with previously described activities suggests that the pore may coincide with the peptide-sensitive channel (PSC) (Thieffry et al. (1988) EMBO J. 7, 1449–1454) as well as with two other activities (Dibanich et al. (1989) Eur. J. Biochem. 181, 703–708; Tedeschi et al. (1987) J. Membr. Biol. 97, 21–29) assigned to the mitochondrial outer membrane. The possible relationship of this channel to the mitochondrial megachannel is discussed.
Journal of Bioenergetics and Biomembranes, 2000
Mitochondrial porin, or VDAC, is a pore-forming protein abundant in the outer mitochondrialmembra... more Mitochondrial porin, or VDAC, is a pore-forming protein abundant in the outer mitochondrialmembrane. Several publications have reported extramitochondrial localizations as well, butthe evidence was considered insufficient by many, and the presence of porin in nonmitochondrialcellular compartments has remained in doubt for a long time. We have now obtained newdata indicating that the plasma membrane of hematopoietic cells contains porin, probablylocated mostly in caveolae or caveolae-like domains. Porin was purified from the plasmamembrane of intact cells by a procedure utilizing the membrane-impermeable labeling reagentNH-SS-biotin and streptavidin affinity chromatography, and shown to have the same propertiesas mitochondrial porin. A channel with properties similar to that of isolated VDAC wasobserved by patch-clamping intact cells. This review discusses the evidence supportingextramitochondrial localization, the putative identification of the plasma membrane porin with the“maxi” chloride channel, the hypothetical mechanisms of sorting porin to various cellularmembrane structures, and its possible functions.
Biochemical and Biophysical Research Communications, 1998
The recent findings that mitochondrial porin, VDAC, participates in supramolecular complexes and ... more The recent findings that mitochondrial porin, VDAC, participates in supramolecular complexes and is present in the plasmamembrane need to be reconciled with its biophysical properties. We report here that VDAC often displays previously unobserved or unappreciated behaviors. Reconstituted VDAC can: a) exhibit fast gating when in any of many conductance substates; b) close completely, although briefly, on its own; c) close for long periods, in the presence of König's polyanion; d) take several milliseconds to re-open when an applied transmembrane potential is switched off; e) be desensitized by prolonged exposure to high voltages, so that it will not re-open to the full conductance state upon subsequent return to zero voltage; f) display polarity-dependent voltage-induced closure. These behaviors are especially noticeable when the observations are conducted on a single reincorporated channel, suggesting that interactions between copies of VDAC may play a role in determining its electrophysiological properties. Any model of VDAC's structure, gating and function should take these observations into account.
The transport of genetic material across biomembranes is a process of great relevance for several... more The transport of genetic material across biomembranes is a process of great relevance for several fields of study. However, much remains to be learned about the mechanisms underlying transport, one of which implies the involvement of proteic DNA-conducting pores. Entry of genetic material into mitochondria has been observed under both physiological and pathological conditions. We report here that double-stranded DNA can move through a planar bilayer membrane containing isolated mitochondrial porin (voltage-dependent anion channel). The transport is driven by the applied electrical field, and the presence of DNA is associated with a decrease of current conduction by the pores. The passage of DNA does not take place if the bilayer has not been doped with any protein or in the presence of both reconstituted porin and anti-porin antibody. Translocation does not occur if the bilayer contains Shigella sonnei maltoporin, gramicidin A channels, or a 30 pS anionselective channel plus other proteins. These results show that mitochondrial porin is capable of mediating the transport of genetic material, revealing a new property of this molecule and futher confirming the idea that DNA can move through proteic pores.-Szabò , I., Bàthori, G., Tombola, F., Coppola, A., Schmehl, I., Brini, M., Ghazi, A., De Pinto, V., Zoratti, M. Double-stranded DNA can be translocated across a planar membrane containing purified mitochondrial porin. FASEB J. 12, 495-502 (1998)
Nanomedicine-nanotechnology Biology and Medicine
induced complement activation and related cardiopulmonary distress in pigs: factors promoting rea... more induced complement activation and related cardiopulmonary distress in pigs: factors promoting reactogenicity of Doxil and AmBisome" (2011).
Biochimica Et Biophysica Acta-general Subjects, 1984
A study was made of the in vitro stability of hemoglobin-containing liposomes (‘hemosomes’) prepa... more A study was made of the in vitro stability of hemoglobin-containing liposomes (‘hemosomes’) prepared from phosphatidylcholines, equimolar cholesterol and red cell lysate by the hand-shaking and ether-injection methods. Absorption spectra indicated hemichrome formation in ‘hemosomes’ prepared by the ether-injection technique, and increased oxidation of hemoglobin in hand-shaken ‘hemosomes’. The denaturation of hemoglobin in ether-injection ‘hemosomes’ was increased if the initial methemoglobin content of the hemolysate, or the temperature of preparation was elevated. It was slower if liposomes were prepared under either N2 or CO, or if the radical scavenger 1,3-diphenylisobenzofuran was added with the ether. Egg phosphatidylcholine and synthetic saturated phospholipids gave the same results. With hand-shaken ‘hemosomes’ the oxidized product was primarily methemoglobin, and oxidation could be inhibited by using saturated phosphatidylcholines instead of egg phosphatidylcholine. Lysophosphatidylcholine levels were higher and arachidonic acid levels lower in egg phosphatidylcholine ‘hemosomes’ than in equivalent liposomes containing no hemolysate. The ‘hemosome’ seems to be a suitable model for the study of hemoglobin-lipid membrane interactions and the resulting hemoglobin denaturation process.
Biochimica Et Biophysica Acta-biomembranes, 1993
The pore-forming protein porin has been isolated from rat heart mitochondria and reconstituted in... more The pore-forming protein porin has been isolated from rat heart mitochondria and reconstituted in phospholipid vesicles of different composition. Rapid release of anions, cations and non-charged molecules has been demonstrated from the proteoliposomes but not from the protein-free liposomes. In spite of its higher molecular mass and charges, the movement of ATP was almost as fast as that of inorganic phosphate. Polyanion (1:2:3 copolymer of methacrylate/maleate/styrene), a potent inhibitor of porin residing in the mitochondrial contact sites decreased the solute movements but did not completely block any of the investigated transport processes (phosphate, chloride, ATP). Alterations of the lipid environment had significant effect: an increase in the proportion of soybean phospholipids to egg yolk phospholipids resulted in a decrease in the amount of transported substance but did not fully inhibit the ion movements. It is concluded that the transport properties of porin reconstituted in artificial phospholipid membranes are different from the characteristics of porin prevailing in the mitochondrial contact sites and additional regulatory factors are suggested to be effective in the intact mitochondria.
Biochimica Et Biophysica Acta-biomembranes, 1995
Transport properties of mitochondrial porin were investigated on the basis of changes in the acti... more Transport properties of mitochondrial porin were investigated on the basis of changes in the activity of hexokinase utilizing external ATP. Production of glucose: 6-phosphate is inhibited by polyanion both in intact brain mitochondria and in contact point vesicles. Hexokinase activity is restored by solubilization of the enzyme by high ionic strength or 0.5-1% Triton X-100. In very low concentrations (0.001–0.005%) Triton does not mobilize hexokinase from its binding sites but it is able to release polyanion-inhibition completely. This finding provides an explanation for the discrepancy observed in the transport properties of porin when studied ‘in situ’ or in artificial lipid membranes.
Critical Reviews in Therapeutic Drug Carrier Systems, 2004
Caveolae are bottleshape-like invaginations of the plasma membrane. After internalization they ar... more Caveolae are bottleshape-like invaginations of the plasma membrane. After internalization they are involved in endocytosis, transcytosis, potocytosis, and pinocytosis. Our recently expanded knowledge has made clear that various molecules and macromolecular complexes enter the cells after docking on caveolar receptors, before subsequent internalization of the caveolae. The internalization is initiated by the ligand receptor interaction. Folate, cholesterol, serum lipoproteins, and liposomes are among the most common examples. It is important to point out that, in contrast to the classic clathrin-dependent endocytosis, the caveolar internalization pathway seems to avoid the lysosomes. Internalized caveolae fuse with caveosomes, and the caveosomes deliver their contents into other subcellular (non-lysosomal) compartments. The bypass of the acidic and harmful milieu might be a major advantage for drug delivery via the caveolar pathway. Not all cell types have caveolae. Cells, where the Caveolin I protein is not expressed, do not develop caveolar invaginations. However, these cells have caveolar-equivalent plasma membrane domains, so-called "lipid rafts." Lipid rafts are assembled from the same lipid constituents and proteins as caveolae, but they are flat. Specific ligands may also dock on appropriate receptors of the raft domain. As a complication, certain types of ligand-covered raft receptors can migrate to clathrin-coated pits and get internalized via clathrin-coated vesicles. Nevertheless, suitable ligands or antibodies developed against proteins of the caveolar/raft domains may selectively direct the attached drug carrier to the less harmful caveolar/raft pathway. Thus, understanding of caveolar transport may help in the rational design of more effective drug carriers.
Journal of Bioenergetics and Biomembranes, 1996
The high-conductance channels present in the outer membranes of wild-type and porin-less yeast mi... more The high-conductance channels present in the outer membranes of wild-type and porin-less yeast mitochondria have been characterized electrophysiologically after incorporation in planar bilayer membranes. The most prominent activity was ascribed to a voltage-dependent, substaterich, cationic channel which generally inactivated at potentials positive in thecis compartment, in agreement with the observations from patch-clamp experiments on porin-less mitoplasts. This channel has been identified as the so-called “peptide-sensitive channel” (PSC). We also observed similar channels displaying either no inactivation, or inactivation at both positive and negative potentials. These latter properties match those already described for mammalian and yeast PSC, respectively. These different behaviors are tentatively explained as arising from the presence, or lack of, peptides bound to the PSC. Very high conductances, apparently due to cooperative gating, were frequently displayed. In wild-type membranes, activity ascribable to the porin was also observed.
Biochimica Et Biophysica Acta-biomembranes, 1995
Patch-clamp and planar bilayer experiments on porin-less yeast mitochondria have allowed the char... more Patch-clamp and planar bilayer experiments on porin-less yeast mitochondria have allowed the characterization of a cationic channel activated at matrix-side positive (unphysiological) potentials. In voltage-pulse experiments, inactivation was a faster process than activation and the time constant for inactivation was more steeply dependent on voltage than the one for activation. The channel exhibited various conductance states whose occupancy depended on the applied transmembrane potential. In bilayer experiments, the presence of the pCOx-IV leader peptide induced fast gating in a voltage-dependent manner. A comparison with previously described activities suggests that the pore may coincide with the peptide-sensitive channel (PSC) (Thieffry et al. (1988) EMBO J. 7, 1449–1454) as well as with two other activities (Dibanich et al. (1989) Eur. J. Biochem. 181, 703–708; Tedeschi et al. (1987) J. Membr. Biol. 97, 21–29) assigned to the mitochondrial outer membrane. The possible relationship of this channel to the mitochondrial megachannel is discussed.
Journal of Bioenergetics and Biomembranes, 2000
Mitochondrial porin, or VDAC, is a pore-forming protein abundant in the outer mitochondrialmembra... more Mitochondrial porin, or VDAC, is a pore-forming protein abundant in the outer mitochondrialmembrane. Several publications have reported extramitochondrial localizations as well, butthe evidence was considered insufficient by many, and the presence of porin in nonmitochondrialcellular compartments has remained in doubt for a long time. We have now obtained newdata indicating that the plasma membrane of hematopoietic cells contains porin, probablylocated mostly in caveolae or caveolae-like domains. Porin was purified from the plasmamembrane of intact cells by a procedure utilizing the membrane-impermeable labeling reagentNH-SS-biotin and streptavidin affinity chromatography, and shown to have the same propertiesas mitochondrial porin. A channel with properties similar to that of isolated VDAC wasobserved by patch-clamping intact cells. This review discusses the evidence supportingextramitochondrial localization, the putative identification of the plasma membrane porin with the“maxi” chloride channel, the hypothetical mechanisms of sorting porin to various cellularmembrane structures, and its possible functions.
Biochemical and Biophysical Research Communications, 1998
The recent findings that mitochondrial porin, VDAC, participates in supramolecular complexes and ... more The recent findings that mitochondrial porin, VDAC, participates in supramolecular complexes and is present in the plasmamembrane need to be reconciled with its biophysical properties. We report here that VDAC often displays previously unobserved or unappreciated behaviors. Reconstituted VDAC can: a) exhibit fast gating when in any of many conductance substates; b) close completely, although briefly, on its own; c) close for long periods, in the presence of König's polyanion; d) take several milliseconds to re-open when an applied transmembrane potential is switched off; e) be desensitized by prolonged exposure to high voltages, so that it will not re-open to the full conductance state upon subsequent return to zero voltage; f) display polarity-dependent voltage-induced closure. These behaviors are especially noticeable when the observations are conducted on a single reincorporated channel, suggesting that interactions between copies of VDAC may play a role in determining its electrophysiological properties. Any model of VDAC's structure, gating and function should take these observations into account.
The transport of genetic material across biomembranes is a process of great relevance for several... more The transport of genetic material across biomembranes is a process of great relevance for several fields of study. However, much remains to be learned about the mechanisms underlying transport, one of which implies the involvement of proteic DNA-conducting pores. Entry of genetic material into mitochondria has been observed under both physiological and pathological conditions. We report here that double-stranded DNA can move through a planar bilayer membrane containing isolated mitochondrial porin (voltage-dependent anion channel). The transport is driven by the applied electrical field, and the presence of DNA is associated with a decrease of current conduction by the pores. The passage of DNA does not take place if the bilayer has not been doped with any protein or in the presence of both reconstituted porin and anti-porin antibody. Translocation does not occur if the bilayer contains Shigella sonnei maltoporin, gramicidin A channels, or a 30 pS anionselective channel plus other proteins. These results show that mitochondrial porin is capable of mediating the transport of genetic material, revealing a new property of this molecule and futher confirming the idea that DNA can move through proteic pores.-Szabò , I., Bàthori, G., Tombola, F., Coppola, A., Schmehl, I., Brini, M., Ghazi, A., De Pinto, V., Zoratti, M. Double-stranded DNA can be translocated across a planar membrane containing purified mitochondrial porin. FASEB J. 12, 495-502 (1998)
Nanomedicine-nanotechnology Biology and Medicine
induced complement activation and related cardiopulmonary distress in pigs: factors promoting rea... more induced complement activation and related cardiopulmonary distress in pigs: factors promoting reactogenicity of Doxil and AmBisome" (2011).
Biochimica Et Biophysica Acta-general Subjects, 1984
A study was made of the in vitro stability of hemoglobin-containing liposomes (‘hemosomes’) prepa... more A study was made of the in vitro stability of hemoglobin-containing liposomes (‘hemosomes’) prepared from phosphatidylcholines, equimolar cholesterol and red cell lysate by the hand-shaking and ether-injection methods. Absorption spectra indicated hemichrome formation in ‘hemosomes’ prepared by the ether-injection technique, and increased oxidation of hemoglobin in hand-shaken ‘hemosomes’. The denaturation of hemoglobin in ether-injection ‘hemosomes’ was increased if the initial methemoglobin content of the hemolysate, or the temperature of preparation was elevated. It was slower if liposomes were prepared under either N2 or CO, or if the radical scavenger 1,3-diphenylisobenzofuran was added with the ether. Egg phosphatidylcholine and synthetic saturated phospholipids gave the same results. With hand-shaken ‘hemosomes’ the oxidized product was primarily methemoglobin, and oxidation could be inhibited by using saturated phosphatidylcholines instead of egg phosphatidylcholine. Lysophosphatidylcholine levels were higher and arachidonic acid levels lower in egg phosphatidylcholine ‘hemosomes’ than in equivalent liposomes containing no hemolysate. The ‘hemosome’ seems to be a suitable model for the study of hemoglobin-lipid membrane interactions and the resulting hemoglobin denaturation process.