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DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass

Mitochondrial quality control is essential in highly structured cells such as neurons and muscles. In skeletal muscle the mitochondrial fission proteins are reduced in different physiopathological conditions including ageing sarcopenia, cancer cachexia and chemotherapy-induced muscle wasting. Howeve...

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Autores principales: Favaro, Giulia, Romanello, Vanina, Varanita, Tatiana, Andrea Desbats, Maria, Morbidoni, Valeria, Tezze, Caterina, Albiero, Mattia, Canato, Marta, Gherardi, Gaia, De Stefani, Diego, Mammucari, Cristina, Blaauw, Bert, Boncompagni, Simona, Protasi, Feliciano, Reggiani, Carlo, Scorrano, Luca, Salviati, Leonardo, Sandri, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561930/
https://www.ncbi.nlm.nih.gov/pubmed/31189900
http://dx.doi.org/10.1038/s41467-019-10226-9
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author Favaro, Giulia
Romanello, Vanina
Varanita, Tatiana
Andrea Desbats, Maria
Morbidoni, Valeria
Tezze, Caterina
Albiero, Mattia
Canato, Marta
Gherardi, Gaia
De Stefani, Diego
Mammucari, Cristina
Blaauw, Bert
Boncompagni, Simona
Protasi, Feliciano
Reggiani, Carlo
Scorrano, Luca
Salviati, Leonardo
Sandri, Marco
author_facet Favaro, Giulia
Romanello, Vanina
Varanita, Tatiana
Andrea Desbats, Maria
Morbidoni, Valeria
Tezze, Caterina
Albiero, Mattia
Canato, Marta
Gherardi, Gaia
De Stefani, Diego
Mammucari, Cristina
Blaauw, Bert
Boncompagni, Simona
Protasi, Feliciano
Reggiani, Carlo
Scorrano, Luca
Salviati, Leonardo
Sandri, Marco
author_sort Favaro, Giulia
collection PubMed
description Mitochondrial quality control is essential in highly structured cells such as neurons and muscles. In skeletal muscle the mitochondrial fission proteins are reduced in different physiopathological conditions including ageing sarcopenia, cancer cachexia and chemotherapy-induced muscle wasting. However, whether mitochondrial fission is essential for muscle homeostasis is still unclear. Here we show that muscle-specific loss of the pro-fission dynamin related protein (DRP) 1 induces muscle wasting and weakness. Constitutive Drp1 ablation in muscles reduces growth and causes animal death while inducible deletion results in atrophy and degeneration. Drp1 deficient mitochondria are morphologically bigger and functionally abnormal. The dysfunctional mitochondria signals to the nucleus to induce the ubiquitin-proteasome system and an Unfolded Protein Response while the change of mitochondrial volume results in an increase of mitochondrial Ca(2+) uptake and myofiber death. Our findings reveal that morphology of mitochondrial network is critical for several biological processes that control nuclear programs and Ca(2+) handling.
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spelling pubmed-65619302019-06-21 DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass Favaro, Giulia Romanello, Vanina Varanita, Tatiana Andrea Desbats, Maria Morbidoni, Valeria Tezze, Caterina Albiero, Mattia Canato, Marta Gherardi, Gaia De Stefani, Diego Mammucari, Cristina Blaauw, Bert Boncompagni, Simona Protasi, Feliciano Reggiani, Carlo Scorrano, Luca Salviati, Leonardo Sandri, Marco Nat Commun Article Mitochondrial quality control is essential in highly structured cells such as neurons and muscles. In skeletal muscle the mitochondrial fission proteins are reduced in different physiopathological conditions including ageing sarcopenia, cancer cachexia and chemotherapy-induced muscle wasting. However, whether mitochondrial fission is essential for muscle homeostasis is still unclear. Here we show that muscle-specific loss of the pro-fission dynamin related protein (DRP) 1 induces muscle wasting and weakness. Constitutive Drp1 ablation in muscles reduces growth and causes animal death while inducible deletion results in atrophy and degeneration. Drp1 deficient mitochondria are morphologically bigger and functionally abnormal. The dysfunctional mitochondria signals to the nucleus to induce the ubiquitin-proteasome system and an Unfolded Protein Response while the change of mitochondrial volume results in an increase of mitochondrial Ca(2+) uptake and myofiber death. Our findings reveal that morphology of mitochondrial network is critical for several biological processes that control nuclear programs and Ca(2+) handling. Nature Publishing Group UK 2019-06-12 /pmc/articles/PMC6561930/ /pubmed/31189900 http://dx.doi.org/10.1038/s41467-019-10226-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Favaro, Giulia
Romanello, Vanina
Varanita, Tatiana
Andrea Desbats, Maria
Morbidoni, Valeria
Tezze, Caterina
Albiero, Mattia
Canato, Marta
Gherardi, Gaia
De Stefani, Diego
Mammucari, Cristina
Blaauw, Bert
Boncompagni, Simona
Protasi, Feliciano
Reggiani, Carlo
Scorrano, Luca
Salviati, Leonardo
Sandri, Marco
DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass
title DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass
title_full DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass
title_fullStr DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass
title_full_unstemmed DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass
title_short DRP1-mediated mitochondrial shape controls calcium homeostasis and muscle mass
title_sort drp1-mediated mitochondrial shape controls calcium homeostasis and muscle mass
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561930/
https://www.ncbi.nlm.nih.gov/pubmed/31189900
http://dx.doi.org/10.1038/s41467-019-10226-9
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