Autophagy-Dependent Shuttling of TBC1D5 Controls Plasma Membrane Translocation of GLUT1 and Glucose Uptake.

ABSTRACT: 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 endolysosom

SUBMITTER: Roy S 

PROVIDER: S-EPMC5522182 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature