While endothelial cell (EC) function is affected by mitochondrial metabolic process, the function of mitochondrial dynamics in angiogenesis, the development of recent bloodstream vessels from existing vasculature, is unknown. Ideas reveal that the interior mitochondrial membrane mitochondrial fusion protein optic atrophy 1 (OPA1) is needed for angiogenesis. As a result of angiogenic stimuli, OPA1 levels quickly increase to limit nuclear factor kappa-light-chain-enhancer of activated B cell (NF|êB) signaling, ultimately allowing angiogenic genes expression and angiogenesis. Endothelial Opa1 is definitely needed within an NF|êB-dependent path required for developmental and tumor angiogenesis, impacting tumor growth and metastatization. An initial-in-class small molecule-specific OPA1 inhibitor confirms that EC Opa1 could be pharmacologically geared to curtail tumor growth. Our data identify Opa1 like a crucial element of physiological and tumor angiogenesis.MYLS22