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Mitochondrial-Targeted Therapies Require Mitophagy to Prevent Oxidative Stress Induced by SOD2 Inactivation in Hypertrophied Cardiomyocytes

Heart failure, mostly associated with cardiac hypertrophy, is a major cause of illness and death. Oxidative stress causes accumulation of reactive oxygen species (ROS), leading to mitochondrial dysfunction, suggesting that mitochondria-targeted therapies could be effective in this context. The purpo...

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Autores principales: Peugnet, Victoriane, Chwastyniak, Maggy, Mulder, Paul, Lancel, Steve, Bultot, Laurent, Fourny, Natacha, Renguet, Edith, Bugger, Heiko, Beseme, Olivia, Loyens, Anne, Heyse, Wilfried, Richard, Vincent, Amouyel, Philippe, Bertrand, Luc, Pinet, Florence, Dubois-Deruy, Emilie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029275/
https://www.ncbi.nlm.nih.gov/pubmed/35453408
http://dx.doi.org/10.3390/antiox11040723
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author Peugnet, Victoriane
Chwastyniak, Maggy
Mulder, Paul
Lancel, Steve
Bultot, Laurent
Fourny, Natacha
Renguet, Edith
Bugger, Heiko
Beseme, Olivia
Loyens, Anne
Heyse, Wilfried
Richard, Vincent
Amouyel, Philippe
Bertrand, Luc
Pinet, Florence
Dubois-Deruy, Emilie
author_facet Peugnet, Victoriane
Chwastyniak, Maggy
Mulder, Paul
Lancel, Steve
Bultot, Laurent
Fourny, Natacha
Renguet, Edith
Bugger, Heiko
Beseme, Olivia
Loyens, Anne
Heyse, Wilfried
Richard, Vincent
Amouyel, Philippe
Bertrand, Luc
Pinet, Florence
Dubois-Deruy, Emilie
author_sort Peugnet, Victoriane
collection PubMed
description Heart failure, mostly associated with cardiac hypertrophy, is a major cause of illness and death. Oxidative stress causes accumulation of reactive oxygen species (ROS), leading to mitochondrial dysfunction, suggesting that mitochondria-targeted therapies could be effective in this context. The purpose of this work was to determine whether mitochondria-targeted therapies could improve cardiac hypertrophy induced by mitochondrial ROS. We used neonatal (NCMs) and adult (ACMs) rat cardiomyocytes hypertrophied by isoproterenol (Iso) to induce mitochondrial ROS. A decreased interaction between sirtuin 3 and superoxide dismutase 2 (SOD2) induced SOD2 acetylation on lysine 68 and inactivation, leading to mitochondrial oxidative stress and dysfunction and hypertrophy after 24 h of Iso treatment. To counteract these mechanisms, we evaluated the impact of the mitochondria-targeted antioxidant mitoquinone (MitoQ). MitoQ decreased mitochondrial ROS and hypertrophy in Iso-treated NCMs and ACMs but altered mitochondrial structure and function by decreasing mitochondrial respiration and mitophagy. The same decrease in mitophagy was found in human cardiomyocytes but not in fibroblasts, suggesting a cardiomyocyte-specific deleterious effect of MitoQ. Our data showed the importance of mitochondrial oxidative stress in the development of cardiomyocyte hypertrophy. We observed that targeting mitochondria by MitoQ in cardiomyocytes impaired the metabolism through defective mitophagy, leading to accumulation of deficient mitochondria.
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spelling pubmed-90292752022-04-23 Mitochondrial-Targeted Therapies Require Mitophagy to Prevent Oxidative Stress Induced by SOD2 Inactivation in Hypertrophied Cardiomyocytes Peugnet, Victoriane Chwastyniak, Maggy Mulder, Paul Lancel, Steve Bultot, Laurent Fourny, Natacha Renguet, Edith Bugger, Heiko Beseme, Olivia Loyens, Anne Heyse, Wilfried Richard, Vincent Amouyel, Philippe Bertrand, Luc Pinet, Florence Dubois-Deruy, Emilie Antioxidants (Basel) Article Heart failure, mostly associated with cardiac hypertrophy, is a major cause of illness and death. Oxidative stress causes accumulation of reactive oxygen species (ROS), leading to mitochondrial dysfunction, suggesting that mitochondria-targeted therapies could be effective in this context. The purpose of this work was to determine whether mitochondria-targeted therapies could improve cardiac hypertrophy induced by mitochondrial ROS. We used neonatal (NCMs) and adult (ACMs) rat cardiomyocytes hypertrophied by isoproterenol (Iso) to induce mitochondrial ROS. A decreased interaction between sirtuin 3 and superoxide dismutase 2 (SOD2) induced SOD2 acetylation on lysine 68 and inactivation, leading to mitochondrial oxidative stress and dysfunction and hypertrophy after 24 h of Iso treatment. To counteract these mechanisms, we evaluated the impact of the mitochondria-targeted antioxidant mitoquinone (MitoQ). MitoQ decreased mitochondrial ROS and hypertrophy in Iso-treated NCMs and ACMs but altered mitochondrial structure and function by decreasing mitochondrial respiration and mitophagy. The same decrease in mitophagy was found in human cardiomyocytes but not in fibroblasts, suggesting a cardiomyocyte-specific deleterious effect of MitoQ. Our data showed the importance of mitochondrial oxidative stress in the development of cardiomyocyte hypertrophy. We observed that targeting mitochondria by MitoQ in cardiomyocytes impaired the metabolism through defective mitophagy, leading to accumulation of deficient mitochondria. MDPI 2022-04-06 /pmc/articles/PMC9029275/ /pubmed/35453408 http://dx.doi.org/10.3390/antiox11040723 Text en © 2022 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
Peugnet, Victoriane
Chwastyniak, Maggy
Mulder, Paul
Lancel, Steve
Bultot, Laurent
Fourny, Natacha
Renguet, Edith
Bugger, Heiko
Beseme, Olivia
Loyens, Anne
Heyse, Wilfried
Richard, Vincent
Amouyel, Philippe
Bertrand, Luc
Pinet, Florence
Dubois-Deruy, Emilie
Mitochondrial-Targeted Therapies Require Mitophagy to Prevent Oxidative Stress Induced by SOD2 Inactivation in Hypertrophied Cardiomyocytes
title Mitochondrial-Targeted Therapies Require Mitophagy to Prevent Oxidative Stress Induced by SOD2 Inactivation in Hypertrophied Cardiomyocytes
title_full Mitochondrial-Targeted Therapies Require Mitophagy to Prevent Oxidative Stress Induced by SOD2 Inactivation in Hypertrophied Cardiomyocytes
title_fullStr Mitochondrial-Targeted Therapies Require Mitophagy to Prevent Oxidative Stress Induced by SOD2 Inactivation in Hypertrophied Cardiomyocytes
title_full_unstemmed Mitochondrial-Targeted Therapies Require Mitophagy to Prevent Oxidative Stress Induced by SOD2 Inactivation in Hypertrophied Cardiomyocytes
title_short Mitochondrial-Targeted Therapies Require Mitophagy to Prevent Oxidative Stress Induced by SOD2 Inactivation in Hypertrophied Cardiomyocytes
title_sort mitochondrial-targeted therapies require mitophagy to prevent oxidative stress induced by sod2 inactivation in hypertrophied cardiomyocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029275/
https://www.ncbi.nlm.nih.gov/pubmed/35453408
http://dx.doi.org/10.3390/antiox11040723
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