A tripartite organelle platform links growth factor receptor signaling to mitochondrial metabolism

One open question in the biology of growth factor receptors is how a quantitative input (i.e., ligand concentration) is decoded by the cell to produce specific response(s). Here, we show that an EGFR endocytic mechanism, non-clathrin endocytosis (NCE), which is activated only at high ligand concentr...

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Veröffentlicht in:Nature communications Jg. 15; H. 1; S. 5119 - 19
Hauptverfasser: Mesa, Deborah, Barbieri, Elisa, Raimondi, Andrea, Freddi, Stefano, Miloro, Giorgia, Jendrisek, Gorana, Caldieri, Giusi, Quarto, Micaela, Schiano Lomoriello, Irene, Malabarba, Maria Grazia, Bresci, Arianna, Manetti, Francesco, Vernuccio, Federico, Abdo, Hind, Scita, Giorgio, Lanzetti, Letizia, Polli, Dario, Tacchetti, Carlo, Pinton, Paolo, Bonora, Massimo, Di Fiore, Pier Paolo, Sigismund, Sara
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 15.06.2024
Nature Publishing Group
Nature Portfolio
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Actin
Adenosine Triphosphate - metabolism
Animals
Calcium - metabolism
Calcium ions
Calcium Signaling - physiology
Calcium signalling
Cell Membrane - metabolism
Circuits
Clathrin
Endocytosis
Endoplasmic reticulum
Endoplasmic Reticulum - metabolism
Epidermal growth factor receptors
ErbB Receptors - metabolism
Growth factor receptors
Growth factors
Humanities and Social Sciences
Humans
Ligands
Metabolism
Mitochondria
Mitochondria - metabolism
multidisciplinary
Receptors
Science
Science (multidisciplinary)
Signal Transduction
ISSN:2041-1723, 2041-1723
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Beschreibung
Zusammenfassung:One open question in the biology of growth factor receptors is how a quantitative input (i.e., ligand concentration) is decoded by the cell to produce specific response(s). Here, we show that an EGFR endocytic mechanism, non-clathrin endocytosis (NCE), which is activated only at high ligand concentrations and targets receptor to degradation, requires a tripartite organelle platform involving the plasma membrane (PM), endoplasmic reticulum (ER) and mitochondria. At these contact sites, EGFR-dependent, ER-generated Ca 2+ oscillations are sensed by mitochondria, leading to increased metabolism and ATP production. Locally released ATP is required for cortical actin remodeling and EGFR-NCE vesicle fission. The same biochemical circuitry is also needed for an effector function of EGFR, i.e., collective motility. The multiorganelle signaling platform herein described mediates direct communication between EGFR signaling and mitochondrial metabolism, and is predicted to have a broad impact on cell physiology as it is activated by another growth factor receptor, HGFR/MET. Endocytic control of receptor signaling is emerging as more complex than mere signal attenuation. Here, authors describe an interorganelle platform formed during EGFR endocytosis that allows communication between EGFR and mitochondrial metabolism.
Bibliographie:ObjectType-Article-1
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-49543-z