Shear stress augments mitochondrial ATP generation that triggers ATP release and Ca2+ signaling in vascular endothelial cells

American Journal of Physiology. Heart and Circulatory Physiology
Kimiko YamamotoJ Ando

Abstract

Vascular endothelial cells (ECs) sense and transduce hemodynamic shear stress into intracellular biochemical signals, and Ca2+ signaling plays a critical role in this mechanotransduction, i.e., ECs release ATP in the caveolae in response to shear stress and, in turn, the released ATP activates P2 purinoceptors, which results in an influx into the cells of extracellular Ca2+. However, the mechanism by which the shear stress evokes ATP release remains unclear. Here, we demonstrated that cellular mitochondria play a critical role in this process. Cultured human pulmonary artery ECs were exposed to controlled levels of shear stress in a flow-loading device, and changes in the mitochondrial ATP levels were examined by real-time imaging using a fluorescence resonance energy transfer-based ATP biosensor. Immediately upon exposure of the cells to flow, mitochondrial ATP levels increased, which was both reversible and dependent on the intensity of shear stress. Inhibitors of the mitochondrial electron transport chain and ATP synthase as well as knockdown of caveolin-1, a major structural protein of the caveolae, abolished the shear stress-induced mitochondrial ATP generation, resulting in the loss of ATP release and influx of Ca2+ into ...Continue Reading

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Citations

May 28, 2020·Cells·Giorgia Del Favero, Annette Kraegeloh
Jun 9, 2020·Basic Research in Cardiology·William E HughesDavid D Gutterman
Sep 21, 2020·Journal of Cellular and Molecular Medicine·Florea LupuKenneth Dormer
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Jul 19, 2020·International Journal of Molecular Sciences·Bruno Bragança, Paulo Correia-de-Sá
Dec 16, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kimiko YamamotoJoji Ando
Jan 10, 2021·Current Osteoporosis Reports·Xuehua LiJinhu Xiong
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Maria DudãuMihail E Hinescu
Mar 27, 2021·Nature Reviews. Nephrology·Sébastien J DumasPeter Carmeliet
May 25, 2021·Magnetic Resonance in Medical Sciences : MRMS : an Official Journal of Japan Society of Magnetic Resonance in Medicine·Joji Ando, Kimiko Yamamoto
May 25, 2021·Frontiers in Pharmacology·Qihang KongXiaojing Liu
May 12, 2021·Journal of Biomechanical Engineering·Caymen NovakSamir Ghadiali
Nov 9, 2021·Biochemical Society Transactions·Etienne MorelPatrice Codogno

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Methods Mentioned

BETA
fluorescence
biosensor
transfection

Software Mentioned

MetaMorph
HCImage
Adobe Photoshop

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