Rottenberg, H. The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore. Int. J. Mol. Sci.2023, 24, 12295.
Rottenberg, H. The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore. Int. J. Mol. Sci. 2023, 24, 12295.
Rottenberg, H. The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore. Int. J. Mol. Sci.2023, 24, 12295.
Rottenberg, H. The Reduction in the Mitochondrial Membrane Potential in Aging: The Role of the Mitochondrial Permeability Transition Pore. Int. J. Mol. Sci. 2023, 24, 12295.
Abstract
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 modulate mitochondrial bioenergetics and that this effect is a major cause of aging since artificially increased ∆Ψm in C. elegans increased lifespan. Here I review, critically, studies that reported reduction of ∆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+, thus accelerating degenerative diseases and aging. Since the inhibition of mPTP was shown to restore ∆Ψm and retard aging, the reported lifespan extension by artificially generated ∆Ψm in C. elegans is best explained by inhibition of the voltage-gated mPTP. Similarly, the reported activation of the mitochondrial Unfolded Protein Response by reduction of ∆Ψm, and the reported preservation of ∆Ψm in dietary restriction treatment in C. elegans are best explained as a resulting from activation or inhibition of the voltage-gated mPTP, respectively.
Keywords
Aging, mitochondria, membrane potential, permeability transition pore, C. elegans
Subject
Biology and Life Sciences, Aging
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
