PUBLICATION

The AMPK-Sirtuin 1-YAP axis is regulated by fluid flow intensity and controls autophagy flux in kidney epithelial cells

Authors
Claude-Taupin, A., Isnard, P., Bagattin, A., Kuperwasser, N., Roccio, F., Ruscica, B., Goudin, N., Garfa-Traoré, M., Regnier, A., Turinsky, L., Burtin, M., Foretz, M., Pontoglio, M., Morel, E., Viollet, B., Terzi, F., Codogno, P., Dupont, N.
ID
ZDB-PUB-231206-7
Date
2023
Source
Nature communications   14: 80568056 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Autophagy/physiology
  • Renal Insufficiency, Chronic*/genetics
  • AMP-Activated Protein Kinases
  • Epithelial Cells/physiology
  • Zebrafish
  • Animals
  • Humans
  • Sirtuin 1*/genetics
  • Kidney
  • Mice
(all 10)
PubMed
38052799 Full text @ Nat. Commun.
Abstract
Shear stress generated by 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 flux 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 confirm 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 pathological accelerated flow observed at early stages of chronic kidney disease (CKD) activates YAP, leading to a primary cilium-dependent inhibition of autophagic flux. We confirm this YAP/autophagy relationship in renal biopsies from patients suffering from diabetic kidney disease (DKD), the leading cause of CKD. 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.
Genes / Markers
Figures
Figure Gallery (10 images)
Show all Figures
Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
li1TgTransgenic Insertion
    pd1065TgTransgenic Insertion
      1 - 2 of 2
      Show
      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      No data available
      Fish
      No data available
      Antibodies
      Name Type Antigen Genes Isotypes Host Organism
      Ab1-yap1polyclonalRabbit
      1 - 1 of 1
      Show
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      RFPEFGRFP
      1 - 2 of 2
      Show
      Mapping
      No data available
      Your Input Welcome
      We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
      Citation
      Claude-Taupin, A., Isnard, P., Bagattin, A., Kuperwasser, N., Roccio, F., Ruscica, B., Goudin, N., Garfa-Traoré, M., Regnier, A., Turinsky, L., Burtin, M., Foretz, M., Pontoglio, M., Morel, E., Viollet, B., Terzi, F., Codogno, P., Dupont, N. (2023) The AMPK-Sirtuin 1-YAP axis is regulated by fluid flow intensity and controls autophagy flux in kidney epithelial cells. Nature communications. 14:80568056.