ZFIN ID: ZDB-PUB-200422-176
Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1
Herkenne, S., Ek, O., Zamberlan, M., Pellattiero, A., Chergova, M., Chivite, I., Novotná, E., Rigoni, G., Fonseca, T.B., Samardzic, D., Agnellini, A., Bean, C., Di Benedetto, G., Tiso, N., Argenton, F., Viola, A., Soriano, M.E., Giacomello, M., Ziviani, E., Sales, G., Claret, M., Graupera, M., Scorrano, L.
Date: 2020
Source: Cell Metabolism   31(5): 987-1003.e8 (Journal)
Registered Authors: Argenton, Francesco, Ek, Olivier, Tiso, Natascia
Keywords: NFκB, Opa1, angiogenesis, cancer, fusion-fission, lymphangiogenesis, metastasis, mitochondria, mouse, tumor, zebrafish
MeSH Terms:
  • Animals
  • Cells, Cultured
  • Female
  • GTP Phosphohydrolases/metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitochondria/metabolism*
  • NF-kappa B/metabolism
  • Neoplasms/metabolism*
  • Neovascularization, Pathologic/metabolism*
  • Signal Transduction
  • Zebrafish
PubMed: 32315597 Full text @ Cell Metab.
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.