Breton-Romero 2014 Biochim Biophys Acta
|Bretón-Romero R, Acín-Perez R, Rodríguez-Pascual F, Martínez-Molledo M, Brandes RP, Rial E, Enríquez JA, Lamas S (2014) Laminar shear stress regulates mitochondrial dynamics, bioenergetics responses and PRX3 activation in endothelial cells. Biochim Biophys Acta 1843:2403-13.|
Abstract: Endothelial cells in the vascular system are constantly subjected to the frictional force of shear stress due to the pulsatile nature of blood flow. Although several proteins form part of the shear stress mechano-sensing pathway, the identification of mechano-transducing pathways is largely unknown. Given the increasing evidence for a signaling function of mitochondria in endothelial cells, the aim of this study was to investigate their role as mechano-sensor organelles during laminar shear stress (LSS). We demonstrated that LSS activates intracellular signaling pathways that modulate not only mitochondrial dynamics but also mitochondrial function. At early time points of LSS, the fission-related protein Drp1 was recruited from the cytosol to mitochondria and activated mitochondrial fission. LSS-dependent increase in intracellular Ca2+ concentration was indispensable for mitochondrial fission. As alterations in mitochondrial dynamics have been related to changes in bioenergetics profiles, we studied mitochondrial function after LSS. We found that LSS decreased respiration rate, increased mitochondrial membrane potential and promoted the mitochondrial generation of ROS with the subsequent oxidation and activation of the antioxidant enzyme PRX3. Our data support a novel and active role for mitochondria in endothelial cells as active players, able to transduce the mechanical force of shear stress in the vascular endothelium into a biological response.
• Keywords: Mechanotransduction, Flow, Bioenergetics, Fission, Peroxiredoxins
Labels: MiParea: Respiration, mt-Structure;fission;fusion
Tissue;cell: Endothelial;epithelial;mesothelial cell, HUVEC Preparation: Intact cells
Coupling state: ROUTINE