The mitochondrial shaping protein Optic Atrophy 1 (OPA1) controls angiogenesis, lymphangiogenesis and tumor growth

Mitochondria not only synthesize most of the cellular ATP, but they are also centrally placed in intermediate metabolism Ca2+ signaling, redox homeostasis and apoptosis. The multifunctional inner mitochondrial membrane mitochondrial fusion protein Optic Atrophy 1 (OPA-1) is placed at the crossroad of fusion, cristae biogenesis, metabolism, apoptosis and regulation of cardiomyocyte differentiation, yet the role of mitochondrial dynamics in angiogenesis, the physiological process through which new blood vessels form from preexisting ones, has not been addressed. Here we show that Opa1 is a crucial component of the angiogenetic program. Upon endothelial cells angiogenic stimulation, mitochondria elongate and OPA-1 level increase. Genetic Opa1 ablation signals retrogradely from mitochondria to the nucleus to modify angiogenic genes expression and therefore inhibit all features of angiogenesis. Conditional Opa1 ablation substantiates its role in mouse and zebrafish angiogenesis and in lymphangiogenesis mediated tumor metastatization. Thus, Opa1-dependent mitochondrial dynamics is a targetable component of angiogenesis.