Autophagy and GLUT1 trafficking: an overview of molecular mechanisms

Autophagy is a catabolic process that enables cellular metabolic adaptation in response to nutrient deprivation. It facilitates the degradation of proteins and cellular components within lysosomes to generate essential metabolites. The glucose transporter 1 (GLUT1) is among the proteins that can undergo autophagy-mediated degradation in response to metabolic stimuli. GLUT1 is essential for cellular glucose supply in several tissues. Notably, GLUT1 facilitates glucose transport across the blood-brain barrier, creating a concentration gradient from the bloodstream into the brain’s interstitial fluid. The presence of GLUT1, at the plasma membrane, is the first step in initiating glucose uptake and driving glycolysis inside the cell. Glycolysis can be initiated in response to several stimuli, including glucose availability, autophagy inhibition, and growth factor accessibility. In this review, we highlight recently described mechanisms that govern the subcellular distribution of GLUT1 with a focus on autophagy-mediated trafficking. Understanding how autophagy coordinates GLUT1 sorting in response to metabolic demands may uncover novel therapeutic targets for metabolic disorders characterized by dysregulated GLUT1 trafficking.