Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1

[en] 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.

Research center :

UNIPD - University of Padua

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Herkenne, Stéphanie ; Université de Liège - ULiège > Cancer-Molecular Angiogenesis Laboratory

ek, olivier

Zamberlan, Margherita

Pellatiero, Anna

Chergova, Maya

chivite, L

Novotna, Eliska

Rigoni, Giovanni

Fonseca, Tiago

samardzic, Dijana

More authors (13 more)

Language :

English

Title :

Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1

Publication date :

2020

Journal title :

Cell Metabolism

ISSN :

1550-4131

eISSN :

1932-7420

Publisher :

Cell Press, United States

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]

Available on ORBi :

since 14 January 2021

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