Mitochondria mediated blood-flow mechanosensing in vascular endothelial cells

Abstract

Vascular endothelial cells sense shear stress generated by blood flow and transduce this into ATP release and purinoceptor-mediated Ca²⁺ signaling within the cells, but the mechanism by which the shear stress evokes ATP release remains unclear. Here we demonstrate that the cellular mitochondria play a critical role in this process. Real-time imaging using a fluorescence resonance energy transfer-based ATP biosensor revealed marked augmentation of ATP generation in the mitochondria immediately after the endothelial cells were exposed to flow. This was reversible and dependent on the shear stress intensity. Inhibitors of the mitochondrial electron-transport chain and ATP synthase abolished the shear stress-induced ATP generation, as well as ATP release and the influx of extracellular Ca²⁺ into the cells. These results suggest that endothelial mitochondria have a role in mechanosensing shear stress and transducing it into ATP generation, followed by ATP release and the activation of Ca²⁺ signaling within the cells.