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

Ryouhei Tsutsumi (), Beatrix Ueberheide, Feng-Xia Liang, Benjamin G. Neel, Ryuichi Sakai and Yoshiro Saito
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Ryouhei Tsutsumi: Kitasato University School of Medicine
Beatrix Ueberheide: NYU Grossman School of Medicine, NYU Langone Health
Feng-Xia Liang: NYU Grossman School of Medicine, NYU Langone Health
Benjamin G. Neel: NYU Grossman School of Medicine, NYU Langone Health
Ryuichi Sakai: Kitasato University School of Medicine
Yoshiro Saito: Tohoku University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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. 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.

Date: 2024
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DOI: 10.1038/s41467-024-46971-9

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