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

M. Yu. Vyssokikh, Susanne Holtze, О. А. Аверина, Konstantin G. Lyamzaev, Alisa A. Panteleeva, Maria V. Marey, Roman A. Zinovkin, Fedor F. Severin, Maxim V. Skulachev, Nicolas J. Fasel, Thomas B. Hildebrandt, Vladimir P. Skulachev

2020Proceedings of the National Academy of Sciences171 citationsDOIOpen Access PDF

Abstract

-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.

Topics & Concepts

DepolarizationComponent (thermodynamics)Inner mitochondrial membraneBiophysicsMembrane potentialInner membraneMembraneChemistryMitochondrionCell biologyBiologyPhysicsBiochemistryQuantum mechanicsMitochondrial Function and PathologyNeuroscience and Neuropharmacology ResearchGenetics, Aging, and Longevity in Model Organisms