Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
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
_version_ 1782471731619823616
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
work_keys_str_mv AT rodriguezvargasjosem autophagyrequirespolyadpribosylationdependentampknuclearexport
AT rodriguezmariai autophagyrequirespolyadpribosylationdependentampknuclearexport
AT majuelosmelguizojara autophagyrequirespolyadpribosylationdependentampknuclearexport
AT garciadiazangel autophagyrequirespolyadpribosylationdependentampknuclearexport
AT gonzalezfloresariannys autophagyrequirespolyadpribosylationdependentampknuclearexport
AT lopezrivasabelardo autophagyrequirespolyadpribosylationdependentampknuclearexport
AT viraglaszlo autophagyrequirespolyadpribosylationdependentampknuclearexport
AT illuzzigiuditta autophagyrequirespolyadpribosylationdependentampknuclearexport
AT schreibervalerie autophagyrequirespolyadpribosylationdependentampknuclearexport
AT dantzerfrancoise autophagyrequirespolyadpribosylationdependentampknuclearexport
AT oliverfjavier autophagyrequirespolyadpribosylationdependentampknuclearexport