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Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome

Autophagy protects organelles, cells, and organisms against several stress conditions. Induction of autophagy by resveratrol requires the nicotinamide adenine dinucleotide–dependent deacetylase sirtuin 1 (SIRT1). In this paper, we show that the acetylase inhibitor spermidine stimulates autophagy ind...

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Autores principales: Morselli, Eugenia, Mariño, Guillermo, Bennetzen, Martin V., Eisenberg, Tobias, Megalou, Evgenia, Schroeder, Sabrina, Cabrera, Sandra, Bénit, Paule, Rustin, Pierre, Criollo, Alfredo, Kepp, Oliver, Galluzzi, Lorenzo, Shen, Shensi, Malik, Shoaib Ahmad, Maiuri, Maria Chiara, Horio, Yoshiyuki, López-Otín, Carlos, Andersen, Jens S., Tavernarakis, Nektarios, Madeo, Frank, Kroemer, Guido
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044119/
https://www.ncbi.nlm.nih.gov/pubmed/21339330
http://dx.doi.org/10.1083/jcb.201008167
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author Morselli, Eugenia
Mariño, Guillermo
Bennetzen, Martin V.
Eisenberg, Tobias
Megalou, Evgenia
Schroeder, Sabrina
Cabrera, Sandra
Bénit, Paule
Rustin, Pierre
Criollo, Alfredo
Kepp, Oliver
Galluzzi, Lorenzo
Shen, Shensi
Malik, Shoaib Ahmad
Maiuri, Maria Chiara
Horio, Yoshiyuki
López-Otín, Carlos
Andersen, Jens S.
Tavernarakis, Nektarios
Madeo, Frank
Kroemer, Guido
author_facet Morselli, Eugenia
Mariño, Guillermo
Bennetzen, Martin V.
Eisenberg, Tobias
Megalou, Evgenia
Schroeder, Sabrina
Cabrera, Sandra
Bénit, Paule
Rustin, Pierre
Criollo, Alfredo
Kepp, Oliver
Galluzzi, Lorenzo
Shen, Shensi
Malik, Shoaib Ahmad
Maiuri, Maria Chiara
Horio, Yoshiyuki
López-Otín, Carlos
Andersen, Jens S.
Tavernarakis, Nektarios
Madeo, Frank
Kroemer, Guido
author_sort Morselli, Eugenia
collection PubMed
description Autophagy protects organelles, cells, and organisms against several stress conditions. Induction of autophagy by resveratrol requires the nicotinamide adenine dinucleotide–dependent deacetylase sirtuin 1 (SIRT1). In this paper, we show that the acetylase inhibitor spermidine stimulates autophagy independent of SIRT1 in human and yeast cells as well as in nematodes. Although resveratrol and spermidine ignite autophagy through distinct mechanisms, these compounds stimulate convergent pathways that culminate in concordant modifications of the acetylproteome. Both agents favor convergent deacetylation and acetylation reactions in the cytosol and in the nucleus, respectively. Both resveratrol and spermidine were able to induce autophagy in cytoplasts (enucleated cells). Moreover, a cytoplasm-restricted mutant of SIRT1 could stimulate autophagy, suggesting that cytoplasmic deacetylation reactions dictate the autophagic cascade. At doses at which neither resveratrol nor spermidine stimulated autophagy alone, these agents synergistically induced autophagy. Altogether, these data underscore the importance of an autophagy regulatory network of antagonistic deacetylases and acetylases that can be pharmacologically manipulated.
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spelling pubmed-30441192011-08-21 Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome Morselli, Eugenia Mariño, Guillermo Bennetzen, Martin V. Eisenberg, Tobias Megalou, Evgenia Schroeder, Sabrina Cabrera, Sandra Bénit, Paule Rustin, Pierre Criollo, Alfredo Kepp, Oliver Galluzzi, Lorenzo Shen, Shensi Malik, Shoaib Ahmad Maiuri, Maria Chiara Horio, Yoshiyuki López-Otín, Carlos Andersen, Jens S. Tavernarakis, Nektarios Madeo, Frank Kroemer, Guido J Cell Biol Research Articles Autophagy protects organelles, cells, and organisms against several stress conditions. Induction of autophagy by resveratrol requires the nicotinamide adenine dinucleotide–dependent deacetylase sirtuin 1 (SIRT1). In this paper, we show that the acetylase inhibitor spermidine stimulates autophagy independent of SIRT1 in human and yeast cells as well as in nematodes. Although resveratrol and spermidine ignite autophagy through distinct mechanisms, these compounds stimulate convergent pathways that culminate in concordant modifications of the acetylproteome. Both agents favor convergent deacetylation and acetylation reactions in the cytosol and in the nucleus, respectively. Both resveratrol and spermidine were able to induce autophagy in cytoplasts (enucleated cells). Moreover, a cytoplasm-restricted mutant of SIRT1 could stimulate autophagy, suggesting that cytoplasmic deacetylation reactions dictate the autophagic cascade. At doses at which neither resveratrol nor spermidine stimulated autophagy alone, these agents synergistically induced autophagy. Altogether, these data underscore the importance of an autophagy regulatory network of antagonistic deacetylases and acetylases that can be pharmacologically manipulated. The Rockefeller University Press 2011-02-21 /pmc/articles/PMC3044119/ /pubmed/21339330 http://dx.doi.org/10.1083/jcb.201008167 Text en © 2011 Morselli et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Morselli, Eugenia
Mariño, Guillermo
Bennetzen, Martin V.
Eisenberg, Tobias
Megalou, Evgenia
Schroeder, Sabrina
Cabrera, Sandra
Bénit, Paule
Rustin, Pierre
Criollo, Alfredo
Kepp, Oliver
Galluzzi, Lorenzo
Shen, Shensi
Malik, Shoaib Ahmad
Maiuri, Maria Chiara
Horio, Yoshiyuki
López-Otín, Carlos
Andersen, Jens S.
Tavernarakis, Nektarios
Madeo, Frank
Kroemer, Guido
Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome
title Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome
title_full Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome
title_fullStr Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome
title_full_unstemmed Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome
title_short Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome
title_sort spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044119/
https://www.ncbi.nlm.nih.gov/pubmed/21339330
http://dx.doi.org/10.1083/jcb.201008167
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