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1000 Titel
  • Mild depolarization of the inner mitochondrial membrane is a crucial component of an anti-aging program
1000 Autor/in
  1. Vyssokikh, Mikhail |
  2. Holtze, Susanne |
  3. Averina, Olga A. |
  4. Lyamzaev, Konstantin G. |
  5. Panteleeva, Alisa A. |
  6. Marey, Maria V. |
  7. Zinovkin, Roman A. |
  8. Severin, Fedor F. |
  9. Skulachev, Maxim V. |
  10. Fasel, Nicolas |
  11. Hildebrandt, Thomas Bernd |
  12. Skulachev, Vladimir P. |
1000 Erscheinungsjahr 2020
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-03-09
1000 Erschienen in
1000 Quellenangabe
  • 117(12):6491-6501
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1073/pnas.1916414117 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104298/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • The mitochondria, organelles that produce the largest amounts of ATP and reactive oxygen species (mROS) in living cells, are equipped with a universal mechanism that can completely prevent mROS production. This mechanism consists of mild depolarization of the inner mitochondrial membrane to decrease the membrane potential to a level sufficient to form ATP but insufficient to generate mROS. In short-lived mice, aging is accompanied by inactivation of the mild depolarization mechanism, resulting in chronic poisoning of the organism with mROS. However, mild depolarization still functions for many years in long-lived naked mole rats and bats.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+-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.
1000 Sacherschließung
lokal mitochondria
lokal mild depolarization
lokal antioxidant
lokal aging
lokal naked mole rat
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-4047-6201|https://orcid.org/0000-0002-4654-1916|https://frl.publisso.de/adhoc/uri/QXZlcmluYSwgT2xnYSBBLg==|https://frl.publisso.de/adhoc/uri/THlhbXphZXYsIEtvbnN0YW50aW4gRy4=|https://frl.publisso.de/adhoc/uri/UGFudGVsZWV2YSwgQWxpc2EgQS4=|https://frl.publisso.de/adhoc/uri/TWFyZXksIE1hcmlhIFYu|https://frl.publisso.de/adhoc/uri/Wmlub3ZraW4sIFJvbWFuIEEu|https://frl.publisso.de/adhoc/uri/U2V2ZXJpbiwgRmVkb3IgRi4=|https://frl.publisso.de/adhoc/uri/U2t1bGFjaGV2LCBNYXhpbSBWLg==|https://frl.publisso.de/adhoc/uri/RmFzZWwsIE5pY29sYXM=|https://orcid.org/0000-0001-8685-4733|https://frl.publisso.de/adhoc/uri/U2t1bGFjaGV2LCBWbGFkaW1pciBQLg==
1000 Label
1000 Förderer
  1. Russian Foundation for Basic Research |
  2. Leibniz-Institut für Zoo- und Wildtierforschung |
1000 Fördernummer
  1. 17-04-02112A
  2. -
1000 Förderprogramm
  1. -
  2. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Russian Foundation for Basic Research |
    1000 Förderprogramm -
    1000 Fördernummer 17-04-02112A
  2. 1000 joinedFunding-child
    1000 Förderer Leibniz-Institut für Zoo- und Wildtierforschung |
    1000 Förderprogramm -
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6426945.rdf
1000 Erstellt am 2021-04-20T13:04:57.834+0200
1000 Erstellt von 122
1000 beschreibt frl:6426945
1000 Bearbeitet von 122
1000 Zuletzt bearbeitet Tue Apr 20 13:07:03 CEST 2021
1000 Objekt bearb. Tue Apr 20 13:06:25 CEST 2021
1000 Vgl. frl:6426945
1000 Oai Id
  1. oai:frl.publisso.de:frl:6426945 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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