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Edmundo Chavez - One of the best experts on this subject based on the ideXlab platform.
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protective action of tamoxifen on Carboxyatractyloside induced mitochondrial permeability transition
Life Sciences, 2011Co-Authors: Luz Hernandezesquivel, Noemi Garcia, Cecilia Zazueta, Francisco Correa, Edmundo ChavezAbstract:Abstract Aims Mitochondrial permeability transition is established after massive Ca 2+ accumulation inside the matrix, in addition to an inducer. The closure of the pore can be accomplished by adenosine diphosphate and the immunosuppressant cyclosporin A. Recently, the estrogen antagonist, tamoxifen, has been introduced as an inhibitor of the opening of the permeability transition pore. However, the mechanism by which this drug inhibits pore opening is still under discussion. This work was performed with the purpose of establishing the membrane system involved in tamoxifen-induced pore closure. For this purpose, permeability transition was induced after the addition of Carboxyatractyloside, which is a specific reagent that interacts with the adenine nucleotide translocase. Main methods Permeability transition was assessed by analyzing matrix Ca 2+ release, transmembrane electric gradient, and mitochondrial swelling in aged, as well as in freshly prepared mitochondria. Also, cytochrome c content was analyzed in membrane mitochondria as well as in the supernatant. Key findings In freshly prepared mitochondria, tamoxifen, at the concentration of 10 μM, totally inhibited nonspecific membrane permeability induced by 1 μM Carboxyatractyloside. In addition, tamoxifen inhibited non-specific permeability in aged mitochondria and diminished membrane fluidity. Significance Plausibly, the inhibitory effect of tamoxifen on nonspecific membrane permeability, as induced by Carboxyatractyloside, should be ascribed to a diminution, of membrane fluidity by this drug.
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Protective action of tamoxifen on Carboxyatractyloside-induced mitochondrial permeability transition.
Life sciences, 2011Co-Authors: Luz Hernández-esquivel, Cecilia Zazueta, Noemi Garcia, Francisco Correa, Natalia-pavón, Edmundo ChavezAbstract:Mitochondrial permeability transition is established after massive Ca(2+) accumulation inside the matrix, in addition to an inducer. The closure of the pore can be accomplished by adenosine diphosphate and the immunosuppressant cyclosporin A. Recently, the estrogen antagonist, tamoxifen, has been introduced as an inhibitor of the opening of the permeability transition pore. However, the mechanism by which this drug inhibits pore opening is still under discussion. This work was performed with the purpose of establishing the membrane system involved in tamoxifen-induced pore closure. For this purpose, permeability transition was induced after the addition of Carboxyatractyloside, which is a specific reagent that interacts with the adenine nucleotide translocase. Permeability transition was assessed by analyzing matrix Ca(2+) release, transmembrane electric gradient, and mitochondrial swelling in aged, as well as in freshly prepared mitochondria. Also, cytochrome c content was analyzed in membrane mitochondria as well as in the supernatant. In freshly prepared mitochondria, tamoxifen, at the concentration of 10 μM, totally inhibited nonspecific membrane permeability induced by 1 μM Carboxyatractyloside. In addition, tamoxifen inhibited non-specific permeability in aged mitochondria and diminished membrane fluidity. Plausibly, the inhibitory effect of tamoxifen on nonspecific membrane permeability, as induced by Carboxyatractyloside, should be ascribed to a diminution, of membrane fluidity by this drug. Copyright © 2011 Elsevier Inc. All rights reserved.
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cyclosporin a is unable to inhibit Carboxyatractyloside induced permeability transition in aged mitochondria
Comparative Biochemistry and Physiology C-toxicology & Pharmacology, 2009Co-Authors: Noemi Garcia, Cecilia Zazueta, Natalia Pavón, Eduardo Martinezabundis, Edmundo ChavezAbstract:Abstract We studied the effect of mitochondrial ageing on membrane permeability transition. The results obtained indicate that aged mitochondria are neither able to retain Ca2+ nor to maintain a high transmembrane electric gradient. In addition, aged mitochondria undergo a large amplitude swelling. These dysfunctions were circumvented by the addition of cyclosporin A. Furthermore, it is shown that ageing-induced permeability transition causes oxidative damage on the matrix enzyme aconitase. The observed damage in aged mitochondria requires Ca2+ addition; therefore, it was not seen when Sr2+replaced Ca2+. Two important findings in this work were the fact that despite of the presence of cyclosporin A, Carboxyatractyloside was still able to induce permeability transition, and that ageing induced mitochondrial DNA disruption and release of cytochrome c. It is likely that the membrane's increased permeability is due to the effect of fatty acids, since bovine serum albumin makes mitochondria able to retain Ca2+. However, the possibility that the damage might be the result of oxidative stress cannot be discarded.
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The Effect of N-Ethylmaleimide on Permeability Transition as Induced by Carboxyatractyloside, Agaric Acid, and Oleate
Cell Biochemistry and Biophysics, 2008Co-Authors: Noemi Garcia, Natalia Pavón, Edmundo ChavezAbstract:In this work, we studied the effect of N -ethylmaleimide on permeability transition. The findings indicate that the amine inhibited the effects of Carboxyatractyloside and agaric acid. It is known that these reagents interact with the adenine nucleotide carrier through the cytosolic side. When oleate, which interacts through the matrix side, was used it was found that the amine amplified the effects of oleate on permeability transition. The results also show that N -ethylmaleimide strengthened the inhibition induced by Carboxyatractyloside, agaric acid, and oleate on ADP exchange. Furthermore, it was also found that oleate improved the binding of eosin-5-maleimide on the adenine nucleotide translocase.
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Titration of cardiolipin by either 10-N-nonyl acridine orange or acridine orange sensitizes the adenine nucleotide carrier to permeability transition
Journal of Bioenergetics and Biomembranes, 2008Co-Authors: Edmundo Chavez, Cecilia Zazueta, Noemi Garcia, Natalia Pavón, Eduardo Martínez-abundis, Luz Hernández-esquivelAbstract:Under the action of Carboxyatractyloside or fatty acids, adenine nucleotide translocase switches its function from nucleotide carrier to modulator of the opening of a non-specific pore. In addition to the effect of these agents, this modification in activity is, in some way, dependent on the influence of the lipid milieu of the membrane. Cardiolipin is, among other membrane phospholipids, the one that interacts the most with the translocase. This work shows that 10- N -nonyl acridine orange and acridine orange, probes for this phospholipid, modify the sensitivity of the translocase to Carboxyatractyloside, oleate, and palmitate to induce permeability transition. The results also show that these probes stimulate the release of mitochondrial cytochrome c , and increase labeling of the carrier by eosin 5-maleimide. Based on the aforementioned it is proposed that the increase in sensitivity is due to a conformational change in the translocase, induced by the binding of the probe to cardiolipin.
Noemi Garcia - One of the best experts on this subject based on the ideXlab platform.
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protective action of tamoxifen on Carboxyatractyloside induced mitochondrial permeability transition
Life Sciences, 2011Co-Authors: Luz Hernandezesquivel, Noemi Garcia, Cecilia Zazueta, Francisco Correa, Edmundo ChavezAbstract:Abstract Aims Mitochondrial permeability transition is established after massive Ca 2+ accumulation inside the matrix, in addition to an inducer. The closure of the pore can be accomplished by adenosine diphosphate and the immunosuppressant cyclosporin A. Recently, the estrogen antagonist, tamoxifen, has been introduced as an inhibitor of the opening of the permeability transition pore. However, the mechanism by which this drug inhibits pore opening is still under discussion. This work was performed with the purpose of establishing the membrane system involved in tamoxifen-induced pore closure. For this purpose, permeability transition was induced after the addition of Carboxyatractyloside, which is a specific reagent that interacts with the adenine nucleotide translocase. Main methods Permeability transition was assessed by analyzing matrix Ca 2+ release, transmembrane electric gradient, and mitochondrial swelling in aged, as well as in freshly prepared mitochondria. Also, cytochrome c content was analyzed in membrane mitochondria as well as in the supernatant. Key findings In freshly prepared mitochondria, tamoxifen, at the concentration of 10 μM, totally inhibited nonspecific membrane permeability induced by 1 μM Carboxyatractyloside. In addition, tamoxifen inhibited non-specific permeability in aged mitochondria and diminished membrane fluidity. Significance Plausibly, the inhibitory effect of tamoxifen on nonspecific membrane permeability, as induced by Carboxyatractyloside, should be ascribed to a diminution, of membrane fluidity by this drug.
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Protective action of tamoxifen on Carboxyatractyloside-induced mitochondrial permeability transition.
Life sciences, 2011Co-Authors: Luz Hernández-esquivel, Cecilia Zazueta, Noemi Garcia, Francisco Correa, Natalia-pavón, Edmundo ChavezAbstract:Mitochondrial permeability transition is established after massive Ca(2+) accumulation inside the matrix, in addition to an inducer. The closure of the pore can be accomplished by adenosine diphosphate and the immunosuppressant cyclosporin A. Recently, the estrogen antagonist, tamoxifen, has been introduced as an inhibitor of the opening of the permeability transition pore. However, the mechanism by which this drug inhibits pore opening is still under discussion. This work was performed with the purpose of establishing the membrane system involved in tamoxifen-induced pore closure. For this purpose, permeability transition was induced after the addition of Carboxyatractyloside, which is a specific reagent that interacts with the adenine nucleotide translocase. Permeability transition was assessed by analyzing matrix Ca(2+) release, transmembrane electric gradient, and mitochondrial swelling in aged, as well as in freshly prepared mitochondria. Also, cytochrome c content was analyzed in membrane mitochondria as well as in the supernatant. In freshly prepared mitochondria, tamoxifen, at the concentration of 10 μM, totally inhibited nonspecific membrane permeability induced by 1 μM Carboxyatractyloside. In addition, tamoxifen inhibited non-specific permeability in aged mitochondria and diminished membrane fluidity. Plausibly, the inhibitory effect of tamoxifen on nonspecific membrane permeability, as induced by Carboxyatractyloside, should be ascribed to a diminution, of membrane fluidity by this drug. Copyright © 2011 Elsevier Inc. All rights reserved.
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cyclosporin a is unable to inhibit Carboxyatractyloside induced permeability transition in aged mitochondria
Comparative Biochemistry and Physiology C-toxicology & Pharmacology, 2009Co-Authors: Noemi Garcia, Cecilia Zazueta, Natalia Pavón, Eduardo Martinezabundis, Edmundo ChavezAbstract:Abstract We studied the effect of mitochondrial ageing on membrane permeability transition. The results obtained indicate that aged mitochondria are neither able to retain Ca2+ nor to maintain a high transmembrane electric gradient. In addition, aged mitochondria undergo a large amplitude swelling. These dysfunctions were circumvented by the addition of cyclosporin A. Furthermore, it is shown that ageing-induced permeability transition causes oxidative damage on the matrix enzyme aconitase. The observed damage in aged mitochondria requires Ca2+ addition; therefore, it was not seen when Sr2+replaced Ca2+. Two important findings in this work were the fact that despite of the presence of cyclosporin A, Carboxyatractyloside was still able to induce permeability transition, and that ageing induced mitochondrial DNA disruption and release of cytochrome c. It is likely that the membrane's increased permeability is due to the effect of fatty acids, since bovine serum albumin makes mitochondria able to retain Ca2+. However, the possibility that the damage might be the result of oxidative stress cannot be discarded.
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The flavonoid quercetin induces changes in mitochondrial permeability by inhibiting adenine nucleotide translocase
Journal of Bioenergetics and Biomembranes, 2009Co-Authors: Rosalba Ortega, Noemi GarciaAbstract:This study shows the effects of the flavonoid quercetin on diverse mitochondrial functions, among them membrane permeability. Our findings indicate that the addition of 50 µM quercetin did not produce reactive oxygen derived species; however, it inhibited the oxidative stress induced after the addition of Fe^2/H_2O_2 by about 38%. At this concentration, quercetin also promoted a fast calcium release, inhibited oxidative phosphorylation, stimulated oxygen consumption, and decreased membrane potential. In addition 50 µM quercetin inhibited the adenine nucleotide translocase (ANT) by 46%. These effects induced the opening of the permeability transition pore and release of cytochrome c, by its interaction with a component of the non-specific pore complex, fixed to the carrier in the conformation c, as Carboxyatractyloside does. Quercetin-induced permeability transition pore opening was inhibited by 0.5 µM cyclosporin A, but, interestingly, the release of cytochrome c was not inhibited by the immunosuppressor, as quercetin was found to disrupt the outer membrane.
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The Effect of N-Ethylmaleimide on Permeability Transition as Induced by Carboxyatractyloside, Agaric Acid, and Oleate
Cell Biochemistry and Biophysics, 2008Co-Authors: Noemi Garcia, Natalia Pavón, Edmundo ChavezAbstract:In this work, we studied the effect of N -ethylmaleimide on permeability transition. The findings indicate that the amine inhibited the effects of Carboxyatractyloside and agaric acid. It is known that these reagents interact with the adenine nucleotide carrier through the cytosolic side. When oleate, which interacts through the matrix side, was used it was found that the amine amplified the effects of oleate on permeability transition. The results also show that N -ethylmaleimide strengthened the inhibition induced by Carboxyatractyloside, agaric acid, and oleate on ADP exchange. Furthermore, it was also found that oleate improved the binding of eosin-5-maleimide on the adenine nucleotide translocase.
Cecilia Zazueta - One of the best experts on this subject based on the ideXlab platform.
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protective action of tamoxifen on Carboxyatractyloside induced mitochondrial permeability transition
Life Sciences, 2011Co-Authors: Luz Hernandezesquivel, Noemi Garcia, Cecilia Zazueta, Francisco Correa, Edmundo ChavezAbstract:Abstract Aims Mitochondrial permeability transition is established after massive Ca 2+ accumulation inside the matrix, in addition to an inducer. The closure of the pore can be accomplished by adenosine diphosphate and the immunosuppressant cyclosporin A. Recently, the estrogen antagonist, tamoxifen, has been introduced as an inhibitor of the opening of the permeability transition pore. However, the mechanism by which this drug inhibits pore opening is still under discussion. This work was performed with the purpose of establishing the membrane system involved in tamoxifen-induced pore closure. For this purpose, permeability transition was induced after the addition of Carboxyatractyloside, which is a specific reagent that interacts with the adenine nucleotide translocase. Main methods Permeability transition was assessed by analyzing matrix Ca 2+ release, transmembrane electric gradient, and mitochondrial swelling in aged, as well as in freshly prepared mitochondria. Also, cytochrome c content was analyzed in membrane mitochondria as well as in the supernatant. Key findings In freshly prepared mitochondria, tamoxifen, at the concentration of 10 μM, totally inhibited nonspecific membrane permeability induced by 1 μM Carboxyatractyloside. In addition, tamoxifen inhibited non-specific permeability in aged mitochondria and diminished membrane fluidity. Significance Plausibly, the inhibitory effect of tamoxifen on nonspecific membrane permeability, as induced by Carboxyatractyloside, should be ascribed to a diminution, of membrane fluidity by this drug.
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Protective action of tamoxifen on Carboxyatractyloside-induced mitochondrial permeability transition.
Life sciences, 2011Co-Authors: Luz Hernández-esquivel, Cecilia Zazueta, Noemi Garcia, Francisco Correa, Natalia-pavón, Edmundo ChavezAbstract:Mitochondrial permeability transition is established after massive Ca(2+) accumulation inside the matrix, in addition to an inducer. The closure of the pore can be accomplished by adenosine diphosphate and the immunosuppressant cyclosporin A. Recently, the estrogen antagonist, tamoxifen, has been introduced as an inhibitor of the opening of the permeability transition pore. However, the mechanism by which this drug inhibits pore opening is still under discussion. This work was performed with the purpose of establishing the membrane system involved in tamoxifen-induced pore closure. For this purpose, permeability transition was induced after the addition of Carboxyatractyloside, which is a specific reagent that interacts with the adenine nucleotide translocase. Permeability transition was assessed by analyzing matrix Ca(2+) release, transmembrane electric gradient, and mitochondrial swelling in aged, as well as in freshly prepared mitochondria. Also, cytochrome c content was analyzed in membrane mitochondria as well as in the supernatant. In freshly prepared mitochondria, tamoxifen, at the concentration of 10 μM, totally inhibited nonspecific membrane permeability induced by 1 μM Carboxyatractyloside. In addition, tamoxifen inhibited non-specific permeability in aged mitochondria and diminished membrane fluidity. Plausibly, the inhibitory effect of tamoxifen on nonspecific membrane permeability, as induced by Carboxyatractyloside, should be ascribed to a diminution, of membrane fluidity by this drug. Copyright © 2011 Elsevier Inc. All rights reserved.
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cyclosporin a is unable to inhibit Carboxyatractyloside induced permeability transition in aged mitochondria
Comparative Biochemistry and Physiology C-toxicology & Pharmacology, 2009Co-Authors: Noemi Garcia, Cecilia Zazueta, Natalia Pavón, Eduardo Martinezabundis, Edmundo ChavezAbstract:Abstract We studied the effect of mitochondrial ageing on membrane permeability transition. The results obtained indicate that aged mitochondria are neither able to retain Ca2+ nor to maintain a high transmembrane electric gradient. In addition, aged mitochondria undergo a large amplitude swelling. These dysfunctions were circumvented by the addition of cyclosporin A. Furthermore, it is shown that ageing-induced permeability transition causes oxidative damage on the matrix enzyme aconitase. The observed damage in aged mitochondria requires Ca2+ addition; therefore, it was not seen when Sr2+replaced Ca2+. Two important findings in this work were the fact that despite of the presence of cyclosporin A, Carboxyatractyloside was still able to induce permeability transition, and that ageing induced mitochondrial DNA disruption and release of cytochrome c. It is likely that the membrane's increased permeability is due to the effect of fatty acids, since bovine serum albumin makes mitochondria able to retain Ca2+. However, the possibility that the damage might be the result of oxidative stress cannot be discarded.
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Titration of cardiolipin by either 10-N-nonyl acridine orange or acridine orange sensitizes the adenine nucleotide carrier to permeability transition
Journal of Bioenergetics and Biomembranes, 2008Co-Authors: Edmundo Chavez, Cecilia Zazueta, Noemi Garcia, Natalia Pavón, Eduardo Martínez-abundis, Luz Hernández-esquivelAbstract:Under the action of Carboxyatractyloside or fatty acids, adenine nucleotide translocase switches its function from nucleotide carrier to modulator of the opening of a non-specific pore. In addition to the effect of these agents, this modification in activity is, in some way, dependent on the influence of the lipid milieu of the membrane. Cardiolipin is, among other membrane phospholipids, the one that interacts the most with the translocase. This work shows that 10- N -nonyl acridine orange and acridine orange, probes for this phospholipid, modify the sensitivity of the translocase to Carboxyatractyloside, oleate, and palmitate to induce permeability transition. The results also show that these probes stimulate the release of mitochondrial cytochrome c , and increase labeling of the carrier by eosin 5-maleimide. Based on the aforementioned it is proposed that the increase in sensitivity is due to a conformational change in the translocase, induced by the binding of the probe to cardiolipin.
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Modulation by substrates of the protective effect of cyclosporin A on mitochondrial damage
Life Sciences, 2002Co-Authors: Edmundo Chavez, Cecilia Zazueta, Noemi Garcia, Francisco Correa, César Avilés, Sandra G. Robles, César D Rodrı́guezAbstract:The influence of substrates on the role of cyclosporin A, to promote the closure of the permeability transition pore, was studied. It was found that in succinate-oxidizing mitochondria, cyclosporin inhibited pore opening as induced by Carboxyatractyloside. The opposite occurred when mitochondrial respiration was supported by malate-glutamate, i.e., cyclosporin A was unable to block pore opening promoted by Carboxyatractyloside. We propose that the failure of cyclosporin A to induce pore closure could be due to a low NADH matrix content.
Guy J M Lauquin - One of the best experts on this subject based on the ideXlab platform.
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unambiguous structure of atractyloside and Carboxyatractyloside
ChemInform, 2012Co-Authors: Jeanfrederic Sanchez, Brice Kauffmann, Axelle Grelard, Corinne Sanchez, Veronique Trezeguet, Guy J M LauquinAbstract:In contrast to the hitherto controversial information about the glycon stereostructure in atractyloside (Ia) and Carboxyatractyloside (Ib), the anomeric structure in both diterpenoid glycosides is unambiguously determined by X-ray crystallography studies now.
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unambiguous structure of atractyloside and Carboxyatractyloside
Bioorganic & Medicinal Chemistry Letters, 2012Co-Authors: Jeanfrederic Sanchez, Brice Kauffmann, Axelle Grelard, Corinne Sanchez, Veronique Trezeguet, Guy J M LauquinAbstract:Abstract Atractyloside (ATR) was characterized in 1868 and until now structural studies on diterpenic moiety had been done through the characterization of ATR derivatives; while the glycosidic moiety seemed to be a β- d -glucopyranose a recent crystal structure of the mitochondrial ATP/ADP carrier in complex with CATR showed an α- d -glucopyranose. We decided to re-examine the ATR and CATR structures by crystallographic study of ATR.
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structure of mitochondrial adp atp carrier in complex with Carboxyatractyloside
Nature, 2003Co-Authors: Eva Pebaypeyroula, Guy J M Lauquin, Veronique Trezeguet, Cecile Dahoutgonzalez, Richard Kahn, Gérard BrandolinAbstract:ATP, the principal energy currency of the cell, fuels most biosynthetic reactions in the cytoplasm by its hydrolysis into ADP and inorganic phosphate. Because resynthesis of ATP occurs in the mitochondrial matrix, ATP is exported into the cytoplasm while ADP is imported into the matrix. The exchange is accomplished by a single protein, the ADP/ATP carrier. Here we have solved
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Structure of Mitochondrial Adp/ATP Carrier in Complex with Carboxyatractyloside
Nature, 2003Co-Authors: Eva Pebay-peyroula, Guy J M Lauquin, Veronique Trezeguet, Cécile Dahout-gonzalez, Richard Kahn, Gérard BrandolinAbstract:ATP, the principal energy currency of the cell, fuels most biosynthetic reactions in the cytoplasm by its hydrolysis into ADP and inorganic phosphate. Because resynthesis of ATP occurs in the mitochondrial matrix, ATP is exported into the cytoplasm while ADP is imported into the matrix. The exchange is accomplished by a single protein, the ADP/ATP carrier. Here we have solved
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Structural and Functional Implications of the Instability of the ADP/ATP Transporter Purified from Mitochondria as Revealed by FTIR Spectroscopy
Biophysical Journal, 2003Co-Authors: Víctor A. Lórenz-fonfría, Guy J M Lauquin, Gérard Brandolin, Veronique Trezeguet, Joaquim Villaverde, Esteve PadrósAbstract:The ADP/ATP transporter shows a high instability when solubilized, making it difficult to obtain functional protein with sufficient purity for long-term spectroscopic studies. When solubilized in the detergent dodecyl maltoside the protein is in equilibrium between the so-called CATR and BA conformations and in a few hours it becomes nonfunctional, unable to bind either its inhibitors or its substrates. By Fourier transform infrared spectroscopy, we studied the structural changes involved in this denaturation process. To do so, the Carboxyatractyloside-inhibited protein was used as a structural model for the protein in the CATR conformation and its spectrum was compared with that of the unliganded time-inactivated protein. From the difference spectra of the amide I, amide II, and amide A bands combined with dichroism spectra of the Carboxyatractyloside-inhibited protein, we concluded that few structural differences exist between both states, affecting as few as 11 amino acids (3.5% of the protein); the structural changes consisted in the disappearance of large loop structure and the appearance of aggregated strands. We hypothesize that some mitochondrial loop (tentatively loop M1) shows a high tendency to aggregate, being responsible for the observed features. The functional consequences of this hypothesis are discussed.
Gerhard Gerber - One of the best experts on this subject based on the ideXlab platform.
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The catabolism of endogenous adenine nucleotides in rat liver mitochondria.
Molecular and Cellular Biochemistry, 1990Co-Authors: Mathias Ziegler, Alexander M. Pimenov, Yuri V. Tikhonov, Toguzov Rt, Wolfgang Henke, Wolfgang Dubiel, Gerhard GerberAbstract:The degradation of intramitochondrial adenine nucleotides to nucleosides and bases was investigated by incubating isolated rat liver mitochondria at 37°C under non-phosphorylating conditions in the presence of oligomycin and Carboxyatractyloside. Within 30 min the adenine nucleotides were degraded by about 25 per cent. The main products formed were adenosine and inosine the contents of which increased five- to sevenfold.
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The catabolism of endogenous adenine nucleotides in rat liver mitochondria
Molecular and Cellular Biochemistry, 1990Co-Authors: Mathias Ziegler, Alexander M. Pimenov, Yuri V. Tikhonov, Wolfgang Henke, Wolfgang Dubiel, Ruslan T. Toguzov, Gerhard GerberAbstract:The degradation of intramitochondrial adenine nucleotides to nucleosides and bases was investigated by incubating isolated rat liver mitochondria at 37°C under non-phosphorylating conditions in the presence of oligomycin and Carboxyatractyloside. Within 30 min the adenine nucleotides were degraded by about 25 per cent. The main products formed were adenosine and inosine the contents of which increased five- to sevenfold. Compartmentation studies revealed that about 50 to 60 per cent of the adenosine formed remained inside the organelles whereas inosine was almost completely released into the surrounding medium. Outside the mitochondria only very small amounts of adenine nucleotides were detected. Similar incubations in the presence of [^14C]-adenosine yielded no [^14C]-inosine ruling out extramitochondrial adenosine deamination. It is concluded that endogenous adenine nucleotides can be degraded in mitochondria via AMP dephosphorylation and subsequent adenosine deamination. A purine nucleoside transport system mediating at least the efflux of inosine from the mitochondria is suggested.