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

• Published in: Nature communications Vol. 15; no. 1; pp. 2843 - 15
• Main Authors: Tsutsumi, Ryouhei, Ueberheide, Beatrix, Liang, Feng-Xia, Neel, Benjamin G., Sakai, Ryuichi, Saito, Yoshiro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.04.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/95; 14/19; 14/28; 631/45/320; 631/80/313/1461; 631/80/86/2368; 82/58; 96/35; Cell Membrane - metabolism; Cell membranes; Cell surface; Endocytosis; Enzymes; Fibroblasts; Glucose; Glucose - metabolism; Glucose transporter; Glucose Transporter Type 1 - metabolism; Glycolysis; Growth factors; Humanities and Social Sciences; Kinases; Ligands; Localization; Medicine; Mitochondria; multidisciplinary; Nanoparticles; Phosphorylation; Plasma; Platelet-derived growth factor; Platelet-Derived Growth Factor - metabolism; Proteins; Receptors; Regulatory mechanisms (biology); Science; Science (multidisciplinary); Stimulation; Transport Vesicles - metabolism; Vesicles
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-46971-9

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. Furthermore, 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. Growth factors rapidly raise cellular glycolysis. Here, authors unveil a mechanism where RTK/GLUT1-containing endocytic vesicles deliver glucose to glycolytic enzymes near mitochondria without upregulating cell surface glucose transporters.