Concerted Action of AMPK and Sirtuin-1 Induces Mitochondrial Fragmentation Upon Inhibition of Ca(2+) Transfer to Mitochondria
Mitochondria are highly dynamic organelles constantly undergoing fusion and fission. Ca(2+) regulates many aspects of mitochondrial physiology by modulating the activity of several mitochondrial proteins. We previously showed that inhibition of constitutive IP3R-mediated Ca(2+) transfer to the mitoc...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261923/ https://www.ncbi.nlm.nih.gov/pubmed/32523953 http://dx.doi.org/10.3389/fcell.2020.00378 |
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author | Lovy, Alenka Ahumada-Castro, Ulises Bustos, Galdo Farias, Paula Gonzalez-Billault, Christian Molgó, Jordi Cardenas, Cesar |
author_facet | Lovy, Alenka Ahumada-Castro, Ulises Bustos, Galdo Farias, Paula Gonzalez-Billault, Christian Molgó, Jordi Cardenas, Cesar |
author_sort | Lovy, Alenka |
collection | PubMed |
description | Mitochondria are highly dynamic organelles constantly undergoing fusion and fission. Ca(2+) regulates many aspects of mitochondrial physiology by modulating the activity of several mitochondrial proteins. We previously showed that inhibition of constitutive IP3R-mediated Ca(2+) transfer to the mitochondria leads to a metabolic cellular stress and eventually cell death. Here, we show that the decline of mitochondrial function generated by a lack of Ca(2+) transfer induces a DRP-1 independent mitochondrial fragmentation that at an early time is mediated by an increase in the NAD+/NADH ratio and activation of SIRT1. Subsequently, AMPK predominates and drives the fragmentation. SIRT1 activation leads to the deacetylation of cortactin, favoring actin polymerization, and mitochondrial fragmentation. Knockdown of cortactin or inhibition of actin polymerization prevents fragmentation. These data reveal SIRT1 as a new player in the regulation of mitochondrial fragmentation induced by metabolic/bioenergetic stress through regulating the actin cytoskeleton. |
format | Online Article Text |
id | pubmed-7261923 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72619232020-06-09 Concerted Action of AMPK and Sirtuin-1 Induces Mitochondrial Fragmentation Upon Inhibition of Ca(2+) Transfer to Mitochondria Lovy, Alenka Ahumada-Castro, Ulises Bustos, Galdo Farias, Paula Gonzalez-Billault, Christian Molgó, Jordi Cardenas, Cesar Front Cell Dev Biol Cell and Developmental Biology Mitochondria are highly dynamic organelles constantly undergoing fusion and fission. Ca(2+) regulates many aspects of mitochondrial physiology by modulating the activity of several mitochondrial proteins. We previously showed that inhibition of constitutive IP3R-mediated Ca(2+) transfer to the mitochondria leads to a metabolic cellular stress and eventually cell death. Here, we show that the decline of mitochondrial function generated by a lack of Ca(2+) transfer induces a DRP-1 independent mitochondrial fragmentation that at an early time is mediated by an increase in the NAD+/NADH ratio and activation of SIRT1. Subsequently, AMPK predominates and drives the fragmentation. SIRT1 activation leads to the deacetylation of cortactin, favoring actin polymerization, and mitochondrial fragmentation. Knockdown of cortactin or inhibition of actin polymerization prevents fragmentation. These data reveal SIRT1 as a new player in the regulation of mitochondrial fragmentation induced by metabolic/bioenergetic stress through regulating the actin cytoskeleton. Frontiers Media S.A. 2020-05-25 /pmc/articles/PMC7261923/ /pubmed/32523953 http://dx.doi.org/10.3389/fcell.2020.00378 Text en Copyright © 2020 Lovy, Ahumada-Castro, Bustos, Farias, Gonzalez-Billault, Molgó and Cardenas. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Lovy, Alenka Ahumada-Castro, Ulises Bustos, Galdo Farias, Paula Gonzalez-Billault, Christian Molgó, Jordi Cardenas, Cesar Concerted Action of AMPK and Sirtuin-1 Induces Mitochondrial Fragmentation Upon Inhibition of Ca(2+) Transfer to Mitochondria |
title | Concerted Action of AMPK and Sirtuin-1 Induces Mitochondrial Fragmentation Upon Inhibition of Ca(2+) Transfer to Mitochondria |
title_full | Concerted Action of AMPK and Sirtuin-1 Induces Mitochondrial Fragmentation Upon Inhibition of Ca(2+) Transfer to Mitochondria |
title_fullStr | Concerted Action of AMPK and Sirtuin-1 Induces Mitochondrial Fragmentation Upon Inhibition of Ca(2+) Transfer to Mitochondria |
title_full_unstemmed | Concerted Action of AMPK and Sirtuin-1 Induces Mitochondrial Fragmentation Upon Inhibition of Ca(2+) Transfer to Mitochondria |
title_short | Concerted Action of AMPK and Sirtuin-1 Induces Mitochondrial Fragmentation Upon Inhibition of Ca(2+) Transfer to Mitochondria |
title_sort | concerted action of ampk and sirtuin-1 induces mitochondrial fragmentation upon inhibition of ca(2+) transfer to mitochondria |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261923/ https://www.ncbi.nlm.nih.gov/pubmed/32523953 http://dx.doi.org/10.3389/fcell.2020.00378 |
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