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Autophagy requires poly(adp-ribosyl)ation-dependent AMPK nuclear export
AMPK is a central energy sensor linking extracellular milieu fluctuations with the autophagic machinery. In the current study we uncover that Poly(ADP-ribosyl)ation (PARylation), a post-translational modification (PTM) of proteins, accounts for the spatial and temporal regulation of autophagy by mod...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136490/ https://www.ncbi.nlm.nih.gov/pubmed/27689873 http://dx.doi.org/10.1038/cdd.2016.80 |
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author | Rodríguez-Vargas, José M Rodríguez, María I Majuelos-Melguizo, Jara García-Diaz, Ángel González-Flores, Ariannys López-Rivas, Abelardo Virág, László Illuzzi, Giuditta Schreiber, Valerie Dantzer, Françoise Oliver, F Javier |
author_facet | Rodríguez-Vargas, José M Rodríguez, María I Majuelos-Melguizo, Jara García-Diaz, Ángel González-Flores, Ariannys López-Rivas, Abelardo Virág, László Illuzzi, Giuditta Schreiber, Valerie Dantzer, Françoise Oliver, F Javier |
author_sort | Rodríguez-Vargas, José M |
collection | PubMed |
description | AMPK is a central energy sensor linking extracellular milieu fluctuations with the autophagic machinery. In the current study we uncover that Poly(ADP-ribosyl)ation (PARylation), a post-translational modification (PTM) of proteins, accounts for the spatial and temporal regulation of autophagy by modulating AMPK subcellular localisation and activation. More particularly, we show that the minority AMPK pool needs to be exported to the cytosol in a PARylation-dependent manner for optimal induction of autophagy, including ULK1 phosphorylation and mTORC1 inactivation. PARP-1 forms a molecular complex with AMPK in the nucleus in non-starved cells. In response to nutrient deprivation, PARP-1 catalysed PARylation, induced the dissociation of the PARP-1/AMPK complex and the export of free PARylated nuclear AMPK to the cytoplasm to activate autophagy. PARP inhibition, its silencing or the expression of PARylation-deficient AMPK mutants prevented not only the AMPK nuclear-cytosolic export but also affected the activation of the cytosolic AMPK pool and autophagosome formation. These results demonstrate that PARylation of AMPK is a key early signal to efficiently convey extracellular nutrient perturbations with downstream events needed for the cell to optimize autophagic commitment before autophagosome formation. |
format | Online Article Text |
id | pubmed-5136490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51364902016-12-16 Autophagy requires poly(adp-ribosyl)ation-dependent AMPK nuclear export Rodríguez-Vargas, José M Rodríguez, María I Majuelos-Melguizo, Jara García-Diaz, Ángel González-Flores, Ariannys López-Rivas, Abelardo Virág, László Illuzzi, Giuditta Schreiber, Valerie Dantzer, Françoise Oliver, F Javier Cell Death Differ Original Paper AMPK is a central energy sensor linking extracellular milieu fluctuations with the autophagic machinery. In the current study we uncover that Poly(ADP-ribosyl)ation (PARylation), a post-translational modification (PTM) of proteins, accounts for the spatial and temporal regulation of autophagy by modulating AMPK subcellular localisation and activation. More particularly, we show that the minority AMPK pool needs to be exported to the cytosol in a PARylation-dependent manner for optimal induction of autophagy, including ULK1 phosphorylation and mTORC1 inactivation. PARP-1 forms a molecular complex with AMPK in the nucleus in non-starved cells. In response to nutrient deprivation, PARP-1 catalysed PARylation, induced the dissociation of the PARP-1/AMPK complex and the export of free PARylated nuclear AMPK to the cytoplasm to activate autophagy. PARP inhibition, its silencing or the expression of PARylation-deficient AMPK mutants prevented not only the AMPK nuclear-cytosolic export but also affected the activation of the cytosolic AMPK pool and autophagosome formation. These results demonstrate that PARylation of AMPK is a key early signal to efficiently convey extracellular nutrient perturbations with downstream events needed for the cell to optimize autophagic commitment before autophagosome formation. Nature Publishing Group 2016-12 2016-09-30 /pmc/articles/PMC5136490/ /pubmed/27689873 http://dx.doi.org/10.1038/cdd.2016.80 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Original Paper Rodríguez-Vargas, José M Rodríguez, María I Majuelos-Melguizo, Jara García-Diaz, Ángel González-Flores, Ariannys López-Rivas, Abelardo Virág, László Illuzzi, Giuditta Schreiber, Valerie Dantzer, Françoise Oliver, F Javier Autophagy requires poly(adp-ribosyl)ation-dependent AMPK nuclear export |
title | Autophagy requires poly(adp-ribosyl)ation-dependent AMPK nuclear export |
title_full | Autophagy requires poly(adp-ribosyl)ation-dependent AMPK nuclear export |
title_fullStr | Autophagy requires poly(adp-ribosyl)ation-dependent AMPK nuclear export |
title_full_unstemmed | Autophagy requires poly(adp-ribosyl)ation-dependent AMPK nuclear export |
title_short | Autophagy requires poly(adp-ribosyl)ation-dependent AMPK nuclear export |
title_sort | autophagy requires poly(adp-ribosyl)ation-dependent ampk nuclear export |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136490/ https://www.ncbi.nlm.nih.gov/pubmed/27689873 http://dx.doi.org/10.1038/cdd.2016.80 |
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