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Endocytic vesicles act as vehicles for glucose uptake in response to growth factor stimulation

ABSTRACT: Glycolysis is a fundamental cellular process, yet its regulatory mechanisms remain incompletely understood. Here, we show that a subset of glucose transporter 1 (GLUT1/SLC2A1) co-endocytoses with platelet-derived growth factor (PDGF) receptor (PDGFR) upon PDGF-stimulation. LC-MS was used to characterize the isolates from cells stimulated with PDGF-BB-conjugated nanoparticles (endocytic vesicle fraction) or PDGF-BB plus unconjugated nanoparticles (control). Taken together, multiple glycolytic enzymes localize to these endocytosed PDGFR/GLUT1-containing vesicles adjacent to mitochondria. Contrary to current models, which emphasize the importance of glucose transporters on the cell surface, we find that PDGF-stimulated glucose uptake depends on receptor/transporter endocytosis. Our results suggest that growth factors generate glucose-loaded endocytic vesicles that deliver glucose to the glycolytic machinery in proximity to mitochondria, and argue for a new layer of regulation for glycolytic control governed by cellular membrane dynamics.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Beatrix Ueberheide

PROVIDER: MSV000092208 | MassIVE | Mon Jun 19 12:49:00 BST 2023

SECONDARY ACCESSION(S): PXD043112

REPOSITORIES: MassIVE

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