PUBLICATION
Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1
- Authors
- 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.
- ID
- ZDB-PUB-200422-176
- 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.
Citation
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. (2020) Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1. Cell Metabolism. 31(5):987-1003.e8.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping