Abstract
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.
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Acknowledgements
This study was funded by NIH HL-098976, HL-11174 and HL-122513.
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E.B.-S. contributed conceptually, carried out cell studies, biochemical assays, histology, analysed data and wrote the manuscript; J.I. contributed conceptually and carried out the aorta physiology experiments; H.P. contributed conceptually and analysed images; N.M. made measurements; P.G.A. carried out confocal imaging; T.J.W. analysed images; U.F. contributed conceptually as well as with the human data; B.S. contributed conceptually, made measurements, analysed data and wrote the manuscript.
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Bartolák-Suki, E., Imsirovic, J., Parameswaran, H. et al. Fluctuation-driven mechanotransduction regulates mitochondrial-network structure and function. Nature Mater 14, 1049–1057 (2015). https://doi.org/10.1038/nmat4358
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DOI: https://doi.org/10.1038/nmat4358