Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarization
Summary: An increase in permeability of the mitochondrial inner membrane, mitochondrial permeability transition (PT), is the central event responsible for cell death and tissue damage in conditions such as stroke and heart attack. PT is caused by the cyclosporin A (CSA)-dependent calcium-induced por...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222017199 |
| _version_ | 1798023032540758016 |
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| author | M.A. Neginskaya S.E. Morris E.V. Pavlov |
| author_facet | M.A. Neginskaya S.E. Morris E.V. Pavlov |
| author_sort | M.A. Neginskaya |
| collection | DOAJ |
| description | Summary: An increase in permeability of the mitochondrial inner membrane, mitochondrial permeability transition (PT), is the central event responsible for cell death and tissue damage in conditions such as stroke and heart attack. PT is caused by the cyclosporin A (CSA)-dependent calcium-induced pore, the permeability transition pore (PTP). The molecular details of PTP are incompletely understood. We utilized holographic and fluorescent microscopy to assess the contribution of ATP synthase and adenine nucleotide translocator (ANT) toward PTP. In cells lacking either ATP synthase or ANT, we observed CSA-sensitive membrane depolarization, but not high-conductance PTP. In wild-type cells, calcium-induced CSA-sensitive depolarization preceded opening of PTP, which occurred only after nearly complete mitochondrial membrane depolarization. We propose that both ATP synthase and ANT are required for high-conductance PTP but not depolarization, which presumably occurs through activation of the low-conductance PT, which has a molecular nature that is different from both complexes. |
| first_indexed | 2024-04-11T17:39:41Z |
| format | Article |
| id | doaj.art-37f908378c0f4f6fb0c109eab9f01ad1 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-11T17:39:41Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-37f908378c0f4f6fb0c109eab9f01ad12022-12-22T04:11:31ZengElsevieriScience2589-00422022-11-012511105447Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarizationM.A. Neginskaya0S.E. Morris1E.V. Pavlov2Department of Molecular Pathobiology, New York University, 345 East 24th Street, New York, NY, USA; Corresponding authorDepartment of Molecular Pathobiology, New York University, 345 East 24th Street, New York, NY, USADepartment of Molecular Pathobiology, New York University, 345 East 24th Street, New York, NY, USA; Corresponding authorSummary: An increase in permeability of the mitochondrial inner membrane, mitochondrial permeability transition (PT), is the central event responsible for cell death and tissue damage in conditions such as stroke and heart attack. PT is caused by the cyclosporin A (CSA)-dependent calcium-induced pore, the permeability transition pore (PTP). The molecular details of PTP are incompletely understood. We utilized holographic and fluorescent microscopy to assess the contribution of ATP synthase and adenine nucleotide translocator (ANT) toward PTP. In cells lacking either ATP synthase or ANT, we observed CSA-sensitive membrane depolarization, but not high-conductance PTP. In wild-type cells, calcium-induced CSA-sensitive depolarization preceded opening of PTP, which occurred only after nearly complete mitochondrial membrane depolarization. We propose that both ATP synthase and ANT are required for high-conductance PTP but not depolarization, which presumably occurs through activation of the low-conductance PT, which has a molecular nature that is different from both complexes.http://www.sciencedirect.com/science/article/pii/S2589004222017199Molecular biologyCell biologyFunctional aspects of cell biology |
| spellingShingle | M.A. Neginskaya S.E. Morris E.V. Pavlov Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarization iScience Molecular biology Cell biology Functional aspects of cell biology |
| title | Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarization |
| title_full | Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarization |
| title_fullStr | Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarization |
| title_full_unstemmed | Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarization |
| title_short | Both ANT and ATPase are essential for mitochondrial permeability transition but not depolarization |
| title_sort | both ant and atpase are essential for mitochondrial permeability transition but not depolarization |
| topic | Molecular biology Cell biology Functional aspects of cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222017199 |
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