@misc{10481/110833,
year = {2016},
month = {9},
url = {https://hdl.handle.net/10481/110833},
abstract = {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 nonstarved
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.},
organization = {ASTF 32-2014 (Short-Term Fellowships EMBO Program 2014)},
organization = {Ramón Areces Foundation (Postdoctoral Grants Program 2015)},
organization = {Spanish Ministry of Education Culture and Sport},
organization = {Junta de Andalucía P07-CTS-0239, P10-CTS-0662},
organization = {Spanish Ministry of Economy and Competitiveness SAF2012-40011-C02-01, SAF2015-70520- R, BIO-778, SAF2015-64383-P, RTICC RD12/0036/0026},
organization = {LABEX ANR-10-LABX-0034-Medalis},
publisher = {Springer Nature},
keywords = {Poly ADP-Ribosylation},
keywords = {PARP1},
keywords = {AMPk},
keywords = {Autophagy},
keywords = {Cancer},
title = {Autophagy requires poly(adp-ribosyl)ation-dependent AMPK nuclear export},
doi = {10.1038/cdd.2016.80},
author = {Rodríguez Vargas, José Manuel and Rodríguez, María Isabel and Majuelos-Melguizo, Jara and García-Díaz, Ángel and González-Flores, Arriannys and López-Rivas, Abelardo and Virág, László and Illuzzi, Giuditta and Schreiber, Valérie and Dantzer, Francoise and Oliver, F. Javier},
}