@article{a05f2182852745febecb232948a3825f,
title = "Gαq activation modulates autophagy by promoting mTORC1 signaling",
abstract = "The mTORC1 node plays a major role in autophagy modulation. We report a role of the ubiquitous Gαq subunit, a known transducer of plasma membrane G protein-coupled receptors signaling, as a core modulator of mTORC1 and autophagy. Cells lacking Gαq/11 display higher basal autophagy, enhanced autophagy induction upon different types of nutrient stress along with a decreased mTORC1 activation status. They are also unable to reactivate mTORC1 and thus inactivate ongoing autophagy upon nutrient recovery. Conversely, stimulation of Gαq/11 promotes sustained mTORC1 pathway activation and reversion of autophagy promoted by serum or amino acids removal. Gαq is present in autophagic compartments and lysosomes and is part of the mTORC1 multi-molecular complex, contributing to its assembly and activation via its nutrient status-sensitive interaction with p62, which displays features of a Gαq effector. Gαq emerges as a central regulator of the autophagy machinery required to maintain cellular homeostasis upon nutrient fluctuations.",
author = "Sof{\'i}a Cabezudo and Maria Sanz-Flores and Alvaro Caballero and Inmaculada Tasset and Elena Rebollo and Antonio Diaz and Aragay, {Anna M.} and Cuervo, {Ana Mar{\'i}a} and Federico Mayor and Catalina Ribas",
note = "Funding Information: We thank Paula Ramos, Susana Rojo-Berciano, and Laura L{\'o}pez for helpful technical assistance. Dr. Marta Cruces (Universidad Aut{\'o}noma de Madrid, Spain) for her invaluable help regarding the liver explants experiments, Dr. Badford Berk (University of Rochester, NY, USA) for providing the GFP-Flag-PB1-p62 plasmid, Drs. Stefan Offer-manns and Nina Wettschureck (Max-Planck-Institute for Heart and Lung Research, Germany) for providing Tie2-CreERT2; Gnaq f/f; Gna11−/− [EC-q/11-KO) mice, and Dr. Guzm{\'a}n S{\'a}nchez for scientific advice. We thank also Ricardo Ramos from the Genomic facility of Fundaci{\'o}n Parque Cient{\'i}fico de Madrid (Universidad Aut{\'o}noma de Madrid, Spain) and Gemma Rodr{\'i}guez-Tarduchy from the Genomic facility of the Instituto de Investigaciones Biom{\'e}dicas “Alberto Sols” for their help with cell lines authentication. The help from CBMSO Animal Care, Flow Cytometry, Electron and Optical and Confocal Microscopy facilities is also acknowledged. This work was supported by Ministerio de Econom{\'i}a; Industria y Competitividad (MINECO) of Spain (grant SAF2017-84125-R to F.M.), (grant BFU2017-83379-R to A.M.A.), Instituto de Salud Carlos III (PI18/01662 to CR, co-funded with European FEDER contribution), CIBERCV-Instituto de Salud Carlos III, Spain (grant CB16/11/00278 to F.M., co-funded with European FEDER contribution), Fundaci{\'o}n Ram{\'o}n Areces (to C.R. and F.M.) and Programa de Actividades en Biomedicina de la Comunidad de Madrid-B2017/BMD-3671-INFLAMUNE to F.M. and NIH grants AG021904 and AG038072 to A.M.C. We also acknowledge the support of a Contrato para la Formaci{\'o}n del Profesorado Uni-versitario (FPU13/04341) and (FPU14/06670), an EMBO short-term fellowship (ASTF 600-2016). We also acknowledge institutional support to the CBMSO from Fundaci{\'o}n Ram{\'o}n Areces. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
day = "1",
doi = "10.1038/s41467-021-24811-4",
language = "English (US)",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}