Laminar shear stress regulates mitochondrial dynamics, bioenergetics responses and PRX3 activation in endothelial cells
Laminar shear stress regulates mitochondrial dynamics, bioenergetics responses and PRX3 activation in endothelial cells
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DOI：
10.1016/j.bbamcr.2014.07.003
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发表时间：
2014-11-01
影响因子：
5.1
通讯作者：
Lamas, Santiago
中科院分区：
文献类型：
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作者：
Breton-Romero, Rosa;Acin-Perez, Rebeca;Lamas, Santiago
由于血流的脉动性质，血管系统中的内皮细胞不断受到剪切应力的摩擦力。尽管几种蛋白质构成了剪切应力机械传感途径的一部分，但机械传导途径的识别在很大程度上是未知的。鉴于越来越多的证据表明线粒体在内皮细胞中具有信号传导功能，本研究的目的是研究线粒体在层流剪切应力（LSS）过程中作为机械传感器细胞器的作用。我们证明 LSS 激活细胞内信号通路，不仅调节线粒体动力学，还调节线粒体功能。在 LSS 的早期时间点，裂变相关蛋白 Drp1 从细胞质被招募到线粒体并激活线粒体裂变。 LSS 依赖性细胞内 Ca2+ 浓度的增加对于线粒体裂变是必不可少的。由于线粒体动力学的改变与生物能量学特征的变化有关，我们研究了 LSS 后的线粒体功能。我们发现LSS降低了呼吸速率，增加了线粒体膜电位，并促进线粒体产生ROS，随后氧化和激活抗氧化酶PRX3。我们的数据支持线粒体作为活跃参与者在内皮细胞中发挥新颖而积极的作用，能够将血管内皮剪切应力的机械力转化为生物反应。 (C) 2014 Elsevier B.V. 所有紧身衣保留。
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. (C) 2014 Elsevier B.V. All tights reserved.