Autophagy traditionally sustains metabolism in stressed cells by promoting intracellular catabolism and nutrient recycling. Here, we demonstrate that in response to stresses requiring increased glycolytic demand, the core autophagy machinery also facilitates glucose uptake and glycolytic flux by promoting cell surface expression of the glucose transporter GLUT1/Slc2a1. During metabolic stress, LC3+ autophagic compartments bind and sequester the RabGAP protein TBC1D5 away from its inhibitory interactions with the retromer complex, thereby enabling retromer recruitment to endosome membranes and GLUT1 plasma membrane translocation. In contrast, TBC1D5 inhibitory interactions with the retromer are maintained in autophagy-deficient cells, leading to GLUT1 mis-sorting into endolysosomal compartments. Furthermore, TBC1D5 depletion in autophagy-deficient cells rescues retromer recruitment to endosomal membranes and GLUT1 surface recycling. Hence, TBC1D5 shuttling to autophagosomes during metabolic stress facilitates retromer-dependent GLUT1 trafficking. Overall, our results illuminate key interconnections between the autophagy and endosomal pathways dictating GLUT1 trafficking and extracellular nutrient uptake.
Pubmed ID: 28602638 RIS Download
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