Autophagy exacerbates muscle wasting in cancer cachexia and impairs mitochondrial function

Cancer cachexia is a multifactorial syndrome characterized by anorexia, weight loss and muscle wasting that impairs patients' quality of life and survival. Aim of this work was to evaluate the impact of either autophagy inhibition (knocking down beclin-1) or promotion (overexpressing TP53INP2/D...

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Autores: Penna, Fabio, Ballaro, Riccardo, Martínez Cristóbal, Paula, Sala Cano, David, Sebastián Muñoz, David, Busquets Rius, Sílvia, Muscaritoli, Maurizio, Argilés Huguet, Josep Ma., Costelli, Paola, Zorzano Olarte, Antonio
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/153307
Acesso em linha:https://hdl.handle.net/2445/153307
Access Level:acceso abierto
Palavra-chave:Autofàgia
Caquèxia
Autophagy
Cachexia
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spelling Autophagy exacerbates muscle wasting in cancer cachexia and impairs mitochondrial functionPenna, FabioBallaro, RiccardoMartínez Cristóbal, PaulaSala Cano, DavidSebastián Muñoz, DavidBusquets Rius, SílviaMuscaritoli, MaurizioArgilés Huguet, Josep Ma.Costelli, PaolaZorzano Olarte, AntonioAutofàgiaCaquèxiaAutophagyCachexiaCancer cachexia is a multifactorial syndrome characterized by anorexia, weight loss and muscle wasting that impairs patients' quality of life and survival. Aim of this work was to evaluate the impact of either autophagy inhibition (knocking down beclin-1) or promotion (overexpressing TP53INP2/DOR) on cancer-induced muscle wasting. In C26 tumor-bearing mice, stress-induced autophagy inhibition was unable to rescue the loss of muscle mass and worsened muscle morphology. Treating C26-bearing mice with formoterol, a selective β2-agonist, muscle sparing was paralleled by reduced static autophagy markers, although the flux was maintained. Conversely, the stimulation of muscle autophagy exacerbated muscle atrophy in tumor-bearing mice. TP53INP2 further promoted atrogene expression and suppressed mitochondrial dynamics-related genes. Excessive autophagy might impair mitochondrial function through mitophagy. Consistently, tumor-induced mitochondrial dysfunction was detected by reduced ex vivo muscle fiber respiration. Overall, the results evoke a central role for muscle autophagy in cancer-induced muscle wasting.Elsevier Ltd2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/153307Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1016/j.jmb.2019.05.032Journal of Molecular Biology, 2019, vol. 431, num. 15, p. 2674-2686https://doi.org/10.1016/j.jmb.2019.05.032cc-by-nc-nd (c) Elsevier Ltd, 2019http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1533072026-05-27T06:46:51Z
dc.title.none.fl_str_mv Autophagy exacerbates muscle wasting in cancer cachexia and impairs mitochondrial function
title Autophagy exacerbates muscle wasting in cancer cachexia and impairs mitochondrial function
spellingShingle Autophagy exacerbates muscle wasting in cancer cachexia and impairs mitochondrial function
Penna, Fabio
Autofàgia
Caquèxia
Autophagy
Cachexia
title_short Autophagy exacerbates muscle wasting in cancer cachexia and impairs mitochondrial function
title_full Autophagy exacerbates muscle wasting in cancer cachexia and impairs mitochondrial function
title_fullStr Autophagy exacerbates muscle wasting in cancer cachexia and impairs mitochondrial function
title_full_unstemmed Autophagy exacerbates muscle wasting in cancer cachexia and impairs mitochondrial function
title_sort Autophagy exacerbates muscle wasting in cancer cachexia and impairs mitochondrial function
dc.creator.none.fl_str_mv Penna, Fabio
Ballaro, Riccardo
Martínez Cristóbal, Paula
Sala Cano, David
Sebastián Muñoz, David
Busquets Rius, Sílvia
Muscaritoli, Maurizio
Argilés Huguet, Josep Ma.
Costelli, Paola
Zorzano Olarte, Antonio
author Penna, Fabio
author_facet Penna, Fabio
Ballaro, Riccardo
Martínez Cristóbal, Paula
Sala Cano, David
Sebastián Muñoz, David
Busquets Rius, Sílvia
Muscaritoli, Maurizio
Argilés Huguet, Josep Ma.
Costelli, Paola
Zorzano Olarte, Antonio
author_role author
author2 Ballaro, Riccardo
Martínez Cristóbal, Paula
Sala Cano, David
Sebastián Muñoz, David
Busquets Rius, Sílvia
Muscaritoli, Maurizio
Argilés Huguet, Josep Ma.
Costelli, Paola
Zorzano Olarte, Antonio
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Autofàgia
Caquèxia
Autophagy
Cachexia
topic Autofàgia
Caquèxia
Autophagy
Cachexia
description Cancer cachexia is a multifactorial syndrome characterized by anorexia, weight loss and muscle wasting that impairs patients' quality of life and survival. Aim of this work was to evaluate the impact of either autophagy inhibition (knocking down beclin-1) or promotion (overexpressing TP53INP2/DOR) on cancer-induced muscle wasting. In C26 tumor-bearing mice, stress-induced autophagy inhibition was unable to rescue the loss of muscle mass and worsened muscle morphology. Treating C26-bearing mice with formoterol, a selective β2-agonist, muscle sparing was paralleled by reduced static autophagy markers, although the flux was maintained. Conversely, the stimulation of muscle autophagy exacerbated muscle atrophy in tumor-bearing mice. TP53INP2 further promoted atrogene expression and suppressed mitochondrial dynamics-related genes. Excessive autophagy might impair mitochondrial function through mitophagy. Consistently, tumor-induced mitochondrial dysfunction was detected by reduced ex vivo muscle fiber respiration. Overall, the results evoke a central role for muscle autophagy in cancer-induced muscle wasting.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/153307
url https://hdl.handle.net/2445/153307
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1016/j.jmb.2019.05.032
Journal of Molecular Biology, 2019, vol. 431, num. 15, p. 2674-2686
https://doi.org/10.1016/j.jmb.2019.05.032
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Elsevier Ltd, 2019
http://creativecommons.org/licenses/by-nc-nd/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Elsevier Ltd, 2019
http://creativecommons.org/licenses/by-nc-nd/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier Ltd
publisher.none.fl_str_mv Elsevier Ltd
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,198674

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