G protein-coupled receptors and the regulation of autophagy

• G protein-coupled receptors (GPCRs) can sense nutrients and regulate autophagy.
• GPCRs regulate systemic autophagy by mediating the effects of hormones secreted in response to systemic nutrient fluctuations.
• Downstream effectors of GPCRs that regulate autophagy include: cAMP, Ca2+, IP3, and PI3-kinase.

Autophagy is an important catabolic cellular process that eliminates damaged and unnecessary cytoplasmic proteins and organelles. Basal autophagy occurs during normal physiological conditions, but the activity of this process can be significantly altered in human diseases. Thus, defining the regulatory inputs and signals that control autophagy is essential. Nutrients are key modulators of autophagy. Although autophagy is generally accepted to be regulated in a cell-autonomous fashion, recent studies suggest that nutrients can modulate autophagy in a systemic manner by inducing the secretion of hormones and neurotransmitters that regulate G protein-coupled receptors (GPCRs). Emerging studies show that GPCRs also regulate autophagy by directly detecting extracellular nutrients. We review the role of GPCRs in autophagy regulation, highlighting their potential as therapeutic drug targets.