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Fluctuation-driven mechanotransduction regulates mitochondrial-network structure and function

机译:波动驱动的机械转导调节线粒体网络的结构和功能

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摘要

Cells can be exposed to irregular mechanical fluctuations, such as those arising from changes in blood pressure. Here, we report that ATP production, assessed through changes in mitochondrial membrane potential, is downregulated in vascular smooth muscle cells in culture exposed to monotonous stretch cycles when compared with cells exposed to a variable cyclic stretch that incorporates physiological levels of cycle-by-cycle variability in stretch amplitude. Variable stretch enhances ATP production by increasing the expression of ATP synthase's catalytic domain, cytochrome c oxidase and its tyrosine phosphorylation, mitofusins and PGC-1α. Such a fluctuation-driven mechanotransduction mechanism is mediated by motor proteins and by the enhancement of microtubule-, actin- and mitochondrial-network complexity. We also show that, in aorta rings isolated from rats, monotonous stretch downregulates-whereas variable stretch maintains-physiological vessel-wall contractility through mitochondrial ATP production. Our results have implications for ATP-dependent and mechanosensitive intracellular processes.
机译:细胞可能会遭受不规则的机械波动,例如由于血压变化而引起的波动。在这里,我们报道了通过线粒体膜电位变化评估的ATP产生,与暴露于结合了生理水平逐周期变化的可变循环拉伸的细胞相比,在暴露于单调拉伸循环的培养物中的血管平滑肌细胞被下调。拉伸幅度的可变性。可变延伸通过增加ATP合酶的催化结构域,细胞色素c氧化酶及其酪氨酸磷酸化,丝裂霉素和PGC-1α的表达来增强ATP的产生。这种波动驱动的机械转导机制是由运动蛋白和微管,肌动蛋白和线粒体网络复杂性的增强介导的。我们还显示,在从大鼠中分离出的主动脉环中,单调拉伸下调,而可变拉伸通过线粒体ATP的产生维持生理性血管壁收缩。我们的结果对ATP依赖和机械敏感的细胞内过程具有影响。

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  • 来源
    《Nature Materials》 |2015年第10期|1049-1057|共9页
  • 作者单位

    Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA;

    Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA;

    Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA;

    Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA;

    Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA;

    Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA;

    University Children's Hospital Basel, CH-4031 Basel, Switzerland;

    Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA;

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