Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1
| Autor: | Andrielly H. R. Agnellini, Francesco Argenton, Anna Pellattiero, Maya Chergova, Marc Claret, Luca Scorrano, Giulietta Di Benedetto, Mariona Graupera, Camilla Bean, Marta Giacomello, Olivier Ek, Margherita Zamberlan, Dijana Samardzic, Tiago Branco Fonseca, Antonella Viola, Maria Eugenia Soriano, Gabriele Sales, Natascia Tiso, Stéphanie Herkenne, Giovanni Rigoni, Eliška Novotná, Elena Ziviani, Iñigo Chivite |
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| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Male Physiology Angiogenesis Mitochondrion Opa1 Mitocondris Metastasis GTP Phosphohydrolases angiogenesis Mice 0302 clinical medicine Neoplasms Inner mitochondrial membrane Càncer Cells Cultured Zebrafish Cancer Neovascularization Pathologic NF-kappa B Lymphangiogenesis Cell biology Mitochondria Endothelial stem cell lymphangiogenesis fusion-fission mitochondrial fusion Optic Atrophy 1 Female Signal Transduction tumor endocrine system Mice Transgenic Biology 03 medical and health sciences medicine cancer metastasis Animals Humans Molecular Biology mouse Neovascularization Cell Biology medicine.disease eye diseases Angiogènesi Mice Inbred C57BL 030104 developmental biology NFκB mitochondria zebrafish 030217 neurology & neurosurgery |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Cell Metabolism |
| ISSN: | 1550-4131 |
| DOI: | 10.1016/j.cmet.2020.04.007 |
| Popis: | Summary While endothelial cell (EC) function is influenced by mitochondrial metabolism, the role of mitochondrial dynamics in angiogenesis, the formation of new blood vessels from existing vasculature, is unknown. Here we show that the inner mitochondrial membrane mitochondrial fusion protein optic atrophy 1 (OPA1) is required for angiogenesis. In response to angiogenic stimuli, OPA1 levels rapidly increase to limit nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) signaling, ultimately allowing angiogenic genes expression and angiogenesis. Endothelial Opa1 is indeed required in an NFκB-dependent pathway essential for developmental and tumor angiogenesis, impacting tumor growth and metastatization. A first-in-class small molecule-specific OPA1 inhibitor confirms that EC Opa1 can be pharmacologically targeted to curtail tumor growth. Our data identify Opa1 as a crucial component of physiological and tumor angiogenesis. |
| Databáze: | OpenAIRE |
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