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- Title
A tripartite organelle platform links growth factor receptor signaling to mitochondrial metabolism.
- Authors
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
- Abstract
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 Ca2+ 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.
- Subjects
ENDOCYTOSIS; CELL physiology; METABOLISM; COATED vesicles; MITOCHONDRIA; IMMUNE response; CELL membranes
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-49543-z