The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore
It is widely reported that the mitochondrial membrane potential, ∆Ψm, is reduced in aging animals. It was recently suggested that the lower ∆Ψm in aged animals modulates mitochondrial bioenergetics and that this effect is a major cause of aging since artificially increased ∆Ψm in <i>C. elegans...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/15/12295 |
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| author | Hagai Rottenberg |
| author_facet | Hagai Rottenberg |
| author_sort | Hagai Rottenberg |
| collection | DOAJ |
| description | It is widely reported that the mitochondrial membrane potential, ∆Ψm, is reduced in aging animals. It was recently suggested that the lower ∆Ψm in aged animals modulates mitochondrial bioenergetics and that this effect is a major cause of aging since artificially increased ∆Ψm in <i>C. elegans</i> increased lifespan. Here, I critically review studies that reported reduction in ∆Ψm in aged animals, including worms, and conclude that many of these observations are best interpreted as evidence that the fraction of depolarized mitochondria is increased in aged cells because of the enhanced activation of the mitochondrial permeability transition pore, mPTP. Activation of the voltage-gated mPTP depolarizes the mitochondria, inhibits oxidative phosphorylation, releases large amounts of calcium and mROS, and depletes cellular NAD<sup>+</sup>, thus accelerating degenerative diseases and aging. Since the inhibition of mPTP was shown to restore ∆Ψm and to retard aging, the reported lifespan extension by artificially generated ∆Ψm in <i>C. elegans</i> is best explained by inhibition of the voltage-gated mPTP. Similarly, the reported activation of the mitochondrial unfolded protein response by reduction in ∆Ψm and the reported preservation of ∆Ψm in dietary restriction treatment in <i>C. elegans</i> are best explained as resulting from activation or inhibition of the voltage-gated mPTP, respectively. |
| first_indexed | 2024-03-11T00:25:07Z |
| format | Article |
| id | doaj.art-1f82ca3542e244a3b0d74a55f1b45197 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:25:07Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1f82ca3542e244a3b0d74a55f1b451972023-11-18T23:03:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124151229510.3390/ijms241512295The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition PoreHagai Rottenberg0New Hope Biomedical R&D, 23 W. Bridge Street, New Hope, PA 18938, USAIt is widely reported that the mitochondrial membrane potential, ∆Ψm, is reduced in aging animals. It was recently suggested that the lower ∆Ψm in aged animals modulates mitochondrial bioenergetics and that this effect is a major cause of aging since artificially increased ∆Ψm in <i>C. elegans</i> increased lifespan. Here, I critically review studies that reported reduction in ∆Ψm in aged animals, including worms, and conclude that many of these observations are best interpreted as evidence that the fraction of depolarized mitochondria is increased in aged cells because of the enhanced activation of the mitochondrial permeability transition pore, mPTP. Activation of the voltage-gated mPTP depolarizes the mitochondria, inhibits oxidative phosphorylation, releases large amounts of calcium and mROS, and depletes cellular NAD<sup>+</sup>, thus accelerating degenerative diseases and aging. Since the inhibition of mPTP was shown to restore ∆Ψm and to retard aging, the reported lifespan extension by artificially generated ∆Ψm in <i>C. elegans</i> is best explained by inhibition of the voltage-gated mPTP. Similarly, the reported activation of the mitochondrial unfolded protein response by reduction in ∆Ψm and the reported preservation of ∆Ψm in dietary restriction treatment in <i>C. elegans</i> are best explained as resulting from activation or inhibition of the voltage-gated mPTP, respectively.https://www.mdpi.com/1422-0067/24/15/12295agingmitochondriamembrane potentialpermeability transition pore<i>C. elegans</i> |
| spellingShingle | Hagai Rottenberg The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore International Journal of Molecular Sciences aging mitochondria membrane potential permeability transition pore <i>C. elegans</i> |
| title | The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore |
| title_full | The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore |
| title_fullStr | The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore |
| title_full_unstemmed | The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore |
| title_short | The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore |
| title_sort | reduction in the mitochondrial membrane potential in aging the role of the mitochondrial permeability transition pore |
| topic | aging mitochondria membrane potential permeability transition pore <i>C. elegans</i> |
| url | https://www.mdpi.com/1422-0067/24/15/12295 |
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