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bioRxiv · 10.1101/2023.01.09.523237

YAP-dependent autophagy is controlled by AMPK, SIRT1 and flow intensity in kidney epithelial cells.

Claude-Taupin, A.·Roccio, F.·Garfa-Traore, M.·Regnier, A.·Burtin, M.·Morel, E.·Terzi, F.·Codogno, P.·Dupont, N.
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Abstract

Shear stress generated by the urinary fluid flow is an important regulator of renal function. Its dysregulation is observed in various chronic and acute kidney diseases. Previously, we demonstrated that primary cilium-dependent autophagy allows kidney epithelial cells to adapt their metabolism in response to fluid flow. Here, we show that nuclear YAP/TAZ negatively regulates autophagy machinery in kidney epithelial cells subjected to fluid flow. This crosstalk is supported by a primary cilium-dependent activation of AMPK and SIRT1, independently of the Hippo pathway. We confirmed the relevance of the YAP/TAZ-autophagy molecular dialog in vivo using a zebrafish model of kidney development and a unilateral ureteral obstruction mouse model. In addition, an in vitro assay simulating the pathological flow observed at early stages of chronic kidney disease (CKD) activated YAP, leading to a primary cilium-dependent inhibition of autophagy. Our findings demonstrate the importance of YAP/TAZ and autophagy in the translation of fluid flow into cellular and physiological responses. Dysregulation of this pathway is associated with the early onset of CKD.

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Claude-Taupin, A., Roccio, F., Garfa-Traore, M., Regnier, A., Burtin, M., Morel, E., Terzi, F., Codogno, P., Dupont, N.. 2023-01-09. YAP-dependent autophagy is controlled by AMPK, SIRT1 and flow intensity in kidney epithelial cells.. https://doi.org/10.1101/2023.01.09.523237

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