A hypothetical mechanism capable to reflect the features of the mitochondrial permeability transition pore channel
Mitochondrial permeability transition pore (mPTP) channel plays a central role in cell death because it mediates the effect of a sudden large opening of the inner mitochondrial membrane. Its associations with adenine nucleotide translocase and with ATP synthase within the general framework of mPTP r...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Advances in Redox Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667137924000031 |
| _version_ | 1797260248914853888 |
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| author | Alexander G. Dimitrov |
| author_facet | Alexander G. Dimitrov |
| author_sort | Alexander G. Dimitrov |
| collection | DOAJ |
| description | Mitochondrial permeability transition pore (mPTP) channel plays a central role in cell death because it mediates the effect of a sudden large opening of the inner mitochondrial membrane. Its associations with adenine nucleotide translocase and with ATP synthase within the general framework of mPTP research were challenged by genetic knock out experiments. This paper proposes the hypothesis that the matrix ATP regulates the mPTP. That hypothesis not only succeeds in classifying and explaining the existing experimental data but it also fits quite well to a peripheral branch of mPTP research proposing that the channel is composed of a combination of polyphosphates and poly-(R)-3-hydroxybutyrates glued by Ca ions. ATP also has a polyphosphate part and thus could be potentially incorporated into such kind of a channel. ATP not only has the potential to decrease the effective channel cross-section when the matrix ATP pool is full, but also, having four negative charges, ATP could be driven across the membrane, together with some accompanying metal ions. Thus, an effective potassium hydrogen exchanger is constructed. Cell death and “permeability transition” happen when the matrix ATP pool is emptied and so the mPTP channel is emptied from the ATP. As a result, the effective channel cross-section would greatly increase; instead of effectively going out, potassium would go in, and the matrix would burst. Hence, the regulation of the matrix ATP level could explain the effect of cyclosporin A – the main experimental modulator of mPTP channel activity, the mechanism of hypoxic/reperfusion injury, and many other. |
| first_indexed | 2024-03-08T00:47:38Z |
| format | Article |
| id | doaj.art-018a096873df44a9ae690df45b0fe672 |
| institution | Directory Open Access Journal |
| issn | 2667-1379 |
| language | English |
| last_indexed | 2024-04-24T23:22:19Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Advances in Redox Research |
| spelling | doaj.art-018a096873df44a9ae690df45b0fe6722024-03-16T05:09:55ZengElsevierAdvances in Redox Research2667-13792024-04-0110100096A hypothetical mechanism capable to reflect the features of the mitochondrial permeability transition pore channelAlexander G. Dimitrov0Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 105, Sofia 1113, BulgariaMitochondrial permeability transition pore (mPTP) channel plays a central role in cell death because it mediates the effect of a sudden large opening of the inner mitochondrial membrane. Its associations with adenine nucleotide translocase and with ATP synthase within the general framework of mPTP research were challenged by genetic knock out experiments. This paper proposes the hypothesis that the matrix ATP regulates the mPTP. That hypothesis not only succeeds in classifying and explaining the existing experimental data but it also fits quite well to a peripheral branch of mPTP research proposing that the channel is composed of a combination of polyphosphates and poly-(R)-3-hydroxybutyrates glued by Ca ions. ATP also has a polyphosphate part and thus could be potentially incorporated into such kind of a channel. ATP not only has the potential to decrease the effective channel cross-section when the matrix ATP pool is full, but also, having four negative charges, ATP could be driven across the membrane, together with some accompanying metal ions. Thus, an effective potassium hydrogen exchanger is constructed. Cell death and “permeability transition” happen when the matrix ATP pool is emptied and so the mPTP channel is emptied from the ATP. As a result, the effective channel cross-section would greatly increase; instead of effectively going out, potassium would go in, and the matrix would burst. Hence, the regulation of the matrix ATP level could explain the effect of cyclosporin A – the main experimental modulator of mPTP channel activity, the mechanism of hypoxic/reperfusion injury, and many other.http://www.sciencedirect.com/science/article/pii/S2667137924000031Adenine nucleotide translocaseATP synthaseCyclosporin AK-H exchangerHypoxic/reperfusion injuryCa-H exchanger |
| spellingShingle | Alexander G. Dimitrov A hypothetical mechanism capable to reflect the features of the mitochondrial permeability transition pore channel Advances in Redox Research Adenine nucleotide translocase ATP synthase Cyclosporin A K-H exchanger Hypoxic/reperfusion injury Ca-H exchanger |
| title | A hypothetical mechanism capable to reflect the features of the mitochondrial permeability transition pore channel |
| title_full | A hypothetical mechanism capable to reflect the features of the mitochondrial permeability transition pore channel |
| title_fullStr | A hypothetical mechanism capable to reflect the features of the mitochondrial permeability transition pore channel |
| title_full_unstemmed | A hypothetical mechanism capable to reflect the features of the mitochondrial permeability transition pore channel |
| title_short | A hypothetical mechanism capable to reflect the features of the mitochondrial permeability transition pore channel |
| title_sort | hypothetical mechanism capable to reflect the features of the mitochondrial permeability transition pore channel |
| topic | Adenine nucleotide translocase ATP synthase Cyclosporin A K-H exchanger Hypoxic/reperfusion injury Ca-H exchanger |
| url | http://www.sciencedirect.com/science/article/pii/S2667137924000031 |
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