NOTCH1 and Endothelial Mitochondrial Metabolism

Notch signaling activation drives endothelial-to-mesenchymal transition (EndMT), which is key to heart development. Accumulating evidence indicates that endothelial cell metabolism reprogramming regulates endothelial function independent of canonical cell signaling. Herein, we investigated whether and how Notch signaling and metabolism reprogramming crosstalk in the EndMT process. We found Notch1 intracellular domain (NICD1) was localized within the mitochondria of endothelial cells and interacted with the PDH E1 subunit beta, influencing the phosphorylation of the PDH E1 subunit alpha, thereby activating PDH and enhancing mitochondrial metabolism.