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s41467-023-38292-0.pdf (6.47 MB)

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2023-05-22

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cc by (c) Crosas Molist, Eva et al., 2023
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/201924

AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration

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https://doi.org/10.1038/s41467-023-38292-0

Abstract

Cell migration is crucial for cancer dissemination. We find that AMP-activated protein kinase (AMPK) controls cell migration by acting as an adhesion sensing molecular hub. In 3-dimensional matrices, fast-migrating amoeboid cancer cells exert low adhesion/low traction linked to low ATP/AMP, leading to AMPK activation. In turn, AMPK plays a dual role controlling mitochondrial dynamics and cytoskeletal remodelling. High AMPK activity in low adhering migratory cells, induces mitochondrial fission, resulting in lower oxidative phosphorylation and lower mitochondrial ATP. Concurrently, AMPK inactivates Myosin Phosphatase, increasing Myosin II-dependent amoeboid migration. Reducing adhesion or mitochondrial fusion or activating AMPK induces efficient rounded-amoeboid migration. AMPK inhibition suppresses metastatic potential of amoeboid cancer cells in vivo, while a mitochondrial/AMPK-driven switch is observed in regions of human tumours where amoeboid cells are disseminating. We unveil how mitochondrial dynamics control cell migration and suggest that AMPK is a mechano-metabolic sensor linking energetics and the cytoskeleton. Cell metabolism must adapt to the energy needs of migrating cells. This study finds that fast amoeboid migrating cells harbor high AMPK activity, which controls both mitochondrial dynamics and cytoskeletal remodeling, enabling reduced energy needs.

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Fisiologia cel·lular, Metabolisme cel·lular, Fosforilació

Subject (English)

Cell physiology, Cell metabolism, Phosphorylation

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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CROSAS MOLIST, Eva, et al. AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration. Nature Communications. 2023. Vol. 14, num. 1. ISSN 2041-1723. [consulted: 8 of August of 2026]. Available at: https://hdl.handle.net/2445/201924

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