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Mitochondrial F-ATP Synthase Co-Migrating Proteins and Ca(2+)-Dependent Formation of Large Channels

Monomers, dimers, and individual F(O)F(1)-ATP synthase subunits are, presumably, involved in the formation of the mitochondrial permeability transition pore (PTP), whose molecular structure, however, is still unknown. We hypothesized that, during the Ca(2+)-dependent assembly of a PTP complex, the F...

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Autores principales: Nikiforova, Anna B., Baburina, Yulia L., Borisova, Marina P., Surin, Alexey K., Kharechkina, Ekaterina S., Krestinina, Olga V., Suvorina, Maria Y., Kruglova, Svetlana A., Kruglov, Alexey G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572550/
https://www.ncbi.nlm.nih.gov/pubmed/37830628
http://dx.doi.org/10.3390/cells12192414
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author Nikiforova, Anna B.
Baburina, Yulia L.
Borisova, Marina P.
Surin, Alexey K.
Kharechkina, Ekaterina S.
Krestinina, Olga V.
Suvorina, Maria Y.
Kruglova, Svetlana A.
Kruglov, Alexey G.
author_facet Nikiforova, Anna B.
Baburina, Yulia L.
Borisova, Marina P.
Surin, Alexey K.
Kharechkina, Ekaterina S.
Krestinina, Olga V.
Suvorina, Maria Y.
Kruglova, Svetlana A.
Kruglov, Alexey G.
author_sort Nikiforova, Anna B.
collection PubMed
description Monomers, dimers, and individual F(O)F(1)-ATP synthase subunits are, presumably, involved in the formation of the mitochondrial permeability transition pore (PTP), whose molecular structure, however, is still unknown. We hypothesized that, during the Ca(2+)-dependent assembly of a PTP complex, the F-ATP synthase (subunits) recruits mitochondrial proteins that do not interact or weakly interact with the F-ATP synthase under normal conditions. Therefore, we examined whether the PTP opening in mitochondria before the separation of supercomplexes via BN-PAGE will increase the channel stability and channel-forming capacity of isolated F-ATP synthase dimers and monomers in planar lipid membranes. Additionally, we studied the specific activity and the protein composition of F-ATP synthase dimers and monomers from rat liver and heart mitochondria before and after PTP opening. Against our expectations, preliminary PTP opening dramatically suppressed the high-conductance channel activity of F-ATP synthase dimers and monomers and decreased their specific “in-gel” activity. The decline in the channel-forming activity correlated with the reduced levels of as few as two proteins in the bands: methylmalonate–semialdehyde dehydrogenase and prohibitin 2. These results indicate that proteins co-migrating with the F-ATP synthase may be important players in PTP formation and stabilization.
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spelling pubmed-105725502023-10-14 Mitochondrial F-ATP Synthase Co-Migrating Proteins and Ca(2+)-Dependent Formation of Large Channels Nikiforova, Anna B. Baburina, Yulia L. Borisova, Marina P. Surin, Alexey K. Kharechkina, Ekaterina S. Krestinina, Olga V. Suvorina, Maria Y. Kruglova, Svetlana A. Kruglov, Alexey G. Cells Article Monomers, dimers, and individual F(O)F(1)-ATP synthase subunits are, presumably, involved in the formation of the mitochondrial permeability transition pore (PTP), whose molecular structure, however, is still unknown. We hypothesized that, during the Ca(2+)-dependent assembly of a PTP complex, the F-ATP synthase (subunits) recruits mitochondrial proteins that do not interact or weakly interact with the F-ATP synthase under normal conditions. Therefore, we examined whether the PTP opening in mitochondria before the separation of supercomplexes via BN-PAGE will increase the channel stability and channel-forming capacity of isolated F-ATP synthase dimers and monomers in planar lipid membranes. Additionally, we studied the specific activity and the protein composition of F-ATP synthase dimers and monomers from rat liver and heart mitochondria before and after PTP opening. Against our expectations, preliminary PTP opening dramatically suppressed the high-conductance channel activity of F-ATP synthase dimers and monomers and decreased their specific “in-gel” activity. The decline in the channel-forming activity correlated with the reduced levels of as few as two proteins in the bands: methylmalonate–semialdehyde dehydrogenase and prohibitin 2. These results indicate that proteins co-migrating with the F-ATP synthase may be important players in PTP formation and stabilization. MDPI 2023-10-07 /pmc/articles/PMC10572550/ /pubmed/37830628 http://dx.doi.org/10.3390/cells12192414 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nikiforova, Anna B.
Baburina, Yulia L.
Borisova, Marina P.
Surin, Alexey K.
Kharechkina, Ekaterina S.
Krestinina, Olga V.
Suvorina, Maria Y.
Kruglova, Svetlana A.
Kruglov, Alexey G.
Mitochondrial F-ATP Synthase Co-Migrating Proteins and Ca(2+)-Dependent Formation of Large Channels
title Mitochondrial F-ATP Synthase Co-Migrating Proteins and Ca(2+)-Dependent Formation of Large Channels
title_full Mitochondrial F-ATP Synthase Co-Migrating Proteins and Ca(2+)-Dependent Formation of Large Channels
title_fullStr Mitochondrial F-ATP Synthase Co-Migrating Proteins and Ca(2+)-Dependent Formation of Large Channels
title_full_unstemmed Mitochondrial F-ATP Synthase Co-Migrating Proteins and Ca(2+)-Dependent Formation of Large Channels
title_short Mitochondrial F-ATP Synthase Co-Migrating Proteins and Ca(2+)-Dependent Formation of Large Channels
title_sort mitochondrial f-atp synthase co-migrating proteins and ca(2+)-dependent formation of large channels
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572550/
https://www.ncbi.nlm.nih.gov/pubmed/37830628
http://dx.doi.org/10.3390/cells12192414
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