Shear stress activates mitochondrial oxidative phosphorylation by reducing plasma membrane cholesterol in vascular endothelial cells.

Proceedings of the National Academy of Sciences of the United States of America
Kimiko YamamotoJoji Ando

Abstract

Vascular endothelial cells (ECs) sense and respond to hemodynamic shear stress, which is critical for circulatory homeostasis and the pathophysiology of vascular diseases. The mechanisms of shear stress mechanotransduction, however, remain elusive. We previously demonstrated a direct role of mitochondria in the purinergic signaling of shear stress: shear stress increases mitochondrial adenosine triphosphate (ATP) production, triggering ATP release and Ca2+ signaling via EC purinoceptors. Here, we showed that shear stress rapidly decreases cholesterol in the plasma membrane, thereby activating mitochondrial ATP production. Imaging using domain 4 mutant-derived cholesterol biosensors showed that the application of shear stress to cultured ECs markedly decreased cholesterol levels in both the outer and inner plasma membrane bilayers. Flow cytometry showed that the cholesterol levels in the outer bilayer decreased rapidly after the onset of shear stress, reached a minimum (around 60% of the control level) at 10 min, and plateaued thereafter. After the shear stress ceased, the decreased cholesterol levels returned to those seen in the control. A biochemical analysis showed that shear stress caused both the efflux and the internaliza...Continue Reading

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Citations

May 25, 2021·Magnetic Resonance in Medical Sciences : MRMS : an Official Journal of Japan Society of Magnetic Resonance in Medicine·Joji Ando, Kimiko Yamamoto

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Methods Mentioned

BETA
flow
biosensors
fluorescence
biosensor
fluorescence microscopy
flow cytometry
fluorescence imaging
electrophoresis
Transfection

Software Mentioned

NIS
Adobe Photoshop
HCImage
Image Pro -
SPSS
Kaluza Analysis Flow Cytometry
MetaMorph
Elements C

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