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.
[doi:10.25345/C5445HP25]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Glycolysis ; glucose transporter 1 ; endocytic vesicles
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Principal Investigators: (in alphabetical order) |
Beatrix Ueberheide, NYU School of Medicine, USA |
| Submitting User: | Trixi |
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