title: Laminar shear stress regulates mitochondrial dynamics, bioenergetics responses and PRX3 activation in endothelial cells.
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 Ca(2+) 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.
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus Universidad Autónoma, Nicolás Cabrera 1, E-28049 Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Bretón-Romero
authors.affiliation: Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), E-28029 Madrid, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Acín-Perez
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus Universidad Autónoma, Nicolás Cabrera 1, E-28049 Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez-Pascual
authors.affiliation: Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas - CSIC, E-28040 Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Martínez-Molledo
authors.affiliation: Institut für Kardiovaskuläre Physiologie, Goethe-Universität, 60590 Frankfurt am Main, Germany.
authors.forename: Ralf P
authors.initials: RP
authors.lastname: Brandes
authors.affiliation: Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas - CSIC, E-28040 Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rial
authors.affiliation: Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), E-28029 Madrid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Enríquez
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM, Campus Universidad Autónoma, Nicolás Cabrera 1, E-28049 Madrid, Spain. Electronic address: slamas@cbm.csic.es.
authors.forename: Santiago
authors.initials: S
authors.lastname: Lamas
keywords: Bioenergetics; Fission; Flow; Mechanotransduction; Peroxiredoxins