Mild depolarization of the inner mitochondrial membrane is a crucial component of an anti-aging program.

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Etat: Public
Version: Final published version
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_7F03D9804DEE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Mild depolarization of the inner mitochondrial membrane is a crucial component of an anti-aging program.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Vyssokikh M.Y., Holtze S., Averina O.A., Lyamzaev K.G., Panteleeva A.A., Marey M.V., Zinovkin R.A., Severin F.F., Skulachev M.V., Fasel N., Hildebrandt T.B., Skulachev V.P.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
24/03/2020
Peer-reviewed
Oui
Volume
117
Numéro
12
Pages
6491-6501
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The mitochondria of various tissues from mice, naked mole rats (NMRs), and bats possess two mechanistically similar systems to prevent the generation of mitochondrial reactive oxygen species (mROS): hexokinases I and II and creatine kinase bound to mitochondrial membranes. Both systems operate in a manner such that one of the kinase substrates (mitochondrial ATP) is electrophoretically transported by the ATP/ADP antiporter to the catalytic site of bound hexokinase or bound creatine kinase without ATP dilution in the cytosol. One of the kinase reaction products, ADP, is transported back to the mitochondrial matrix via the antiporter, again through an electrophoretic process without cytosol dilution. The system in question continuously supports H <sup>+</sup> -ATP synthase with ADP until glucose or creatine is available. Under these conditions, the membrane potential, ∆ψ, is maintained at a lower than maximal level (i.e., mild depolarization of mitochondria). This ∆ψ decrease is sufficient to completely inhibit mROS generation. In 2.5-y-old mice, mild depolarization disappears in the skeletal muscles, diaphragm, heart, spleen, and brain and partially in the lung and kidney. This age-dependent decrease in the levels of bound kinases is not observed in NMRs and bats for many years. As a result, ROS-mediated protein damage, which is substantial during the aging of short-lived mice, is stabilized at low levels during the aging of long-lived NMRs and bats. It is suggested that this mitochondrial mild depolarization is a crucial component of the mitochondrial anti-aging system.
Mots-clé
Adenosine Diphosphate/metabolism, Aging, Animals, Chiroptera, Creatine/metabolism, Electron Transport, Embryo, Mammalian, Glucose/metabolism, Hexokinase/metabolism, Membrane Potential, Mitochondrial, Mice, Mitochondria/metabolism, Mitochondria/physiology, Mitochondrial Membranes/enzymology, Mitochondrial Membranes/metabolism, Mitochondrial Membranes/physiology, Mitochondrial Proteins/metabolism, Mole Rats, Organ Specificity, Reactive Oxygen Species/metabolism, Species Specificity, aging, antioxidant, mild depolarization, mitochondria, naked mole rat
Pubmed
Web of science
Open Access
Oui
Création de la notice
30/03/2020 10:51
Dernière modification de la notice
15/01/2021 8:10
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