Fluctuation-driven mechanotransduction regulates mitochondrial-network structure and function
Fluctuation-driven mechanotransduction regulates mitochondrial-network structure and function
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DOI：
10.1038/nmat4358
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发表时间：
2015-10-01
期刊：
影响因子：
41.2
通讯作者：
Suki, Bela
中科院分区：
文献类型：
--
作者：
Bartolak-Suki, Erzsebet;Imsirovic, Jasmin;Suki, Bela
细胞可能会受到不规则的机械波动的影响，例如血压变化引起的波动。在这里，我们报告说，与暴露于可变循环拉伸的细胞相比，通过线粒体膜电位的变化评估的ATP产生在暴露于单调拉伸循环的培养物中的血管平滑肌细胞中被下调，其中可变循环拉伸结合了拉伸幅度的生理水平的逐周期变异性。可变拉伸通过增加 ATP 合酶催化结构域、细胞色素 c 氧化酶及其酪氨酸磷酸化、丝裂融合素和 PGC-1 α 的表达来增强 ATP 产生。这种波动驱动的机械转导机制是由运动蛋白以及微管、肌动蛋白和线粒体网络复杂性的增强介导的。我们还表明，在从大鼠身上分离的主动脉环中，单调拉伸会通过线粒体 ATP 的产生下调生理血管壁收缩性，而可变拉伸则维持生理血管壁收缩性。我们的结果对 ATP 依赖性和机械敏感的细胞内过程具有影响。
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-1 alpha. 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.