G alpha q activation modulates autophagy by promoting mTORC1 signaling

The mTORC1 node plays a major role in autophagy modulation. We report a role of the ubiquitous G alpha q subunit, a known transducer of plasma membrane G protein-coupled receptors signaling, as a core modulator of mTORC1 and autophagy. Cells lacking G alpha q/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 G alpha q/11 promotes sustained mTORC1 pathway activation and reversion of autophagy promoted by serum or amino acids removal. G alpha q 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 G alpha q effector. G alpha q emerges as a central regulator of the autophagy machinery required to maintain cellular homeostasis upon nutrient fluctuations. Nutrient status in the cell regulates autophagy via mTORC1 activity. Here, the authors show that the ubiquitous G protein subunit G alpha q contributes to nutrient sensing by promoting formation of an mTOR-p62-Raptor complex in replete conditions, modulating autophagy.