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

  • bioRxiv. 2023 Jul 24:2023.07.23.550235. doi: 10.1101/2023.07.23.550235.
Ryouhei Tsutsumi  1  2  3 ,  Beatrix Ueberheide  3  4  5 ,  Feng-Xia Liang  3  6 ,  Benjamin G Neel  3 ,  Ryuichi Sakai  1 ,  Yoshiro Saito  2
Affiliations
  • 1. Kitasato University School of Medicine; Sagamihara 252-0374, Kanagawa, Japan.
  • 2. Graduate School of Pharmaceutical Sciences, Tohoku University; Sendai 980-8578, Miyagi, Japan.
  • 3. Perlmutter Cancer Center, NYU Grossman School of Medicine, NYU Langone Health; New York, NY 10016, USA.
  • 4. Proteomics Laboratory, NYU Grossman School of Medicine, NYU Langone Health; New York, NY 10016, USA.
  • 5. Department of Biochemistry and Molecular Pharmacology and Department of Neurology, NYU Grossman School of Medicine, NYU Langone Health; New York, NY 10016, USA.
  • 6. Microscopy Laboratory, NYU Grossman School of Medicine, NYU Langone Health; New York, NY 10016, USA.Paste the full affiliation list here.
PMID: 37546742 DOI: 10.1101/2023.07.23.550235
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.

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