Bienvenu(e) sur le site de l'Institut Necker Enfants Malades
Mercredi 2 septembre 2020
Autophagy and primary cilium in the translation of physical forces to biological responses in kidney.

A work headed by Patrice Codogno and Nicolas Dupont (Team Etienne Morel), recently published in Nature Cell Biology showed the role of shear stress generated by urinary fluid flow on the regulation of the metabolism of epithelial cells from the renal proximal tubular segment. This segment is essential for the reabsorption of low-molecular-weight proteins, metabolites (glucose, amino acids), water and ions. This activity is highly dependent of energy. ATP is produced by mitochondria that consume preferentially fatty acid in this renal segment. In this work, in collaboration with colleagues at INEM (Marco Pontoglio and Fabiola Terzi labs) and the metabolic platform headed by Ivan Nemazanyy (SFR necker), it has been shown that shear stress induces a signaling pathway emanating from the primary cilia. This structure which is present at the apical side of proximal tubule epithelial cells, drives in one hand the induction of mitochondrial biogenesis and on the other hand the stimulation of a selective autophagy (called lipophagy) that selectively targets lipid droplets. This degradation contributes to the production of free fatty acids which are mitochondrial substrates for TCA-cycle to produce energy. This generation of ATP is essential for the main activity of proximal renal cells which are tubular reabsorption and neoglucogenesis. In summary, this study demonstrates the essential role of primary cilium and autophagy in the translation of physical forces (shear stress) into biological response. This work opens new interesting research avenues in the field of renal diseases including chronic kidney diseases which present metabolic alteration and defective tubular flow sensing.


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S.A.R. la Princesse Caroline de Hanovre qui, à travers la Fondation Princesse Grace, soutient déjà la recherche medicale et tout ce qui contribue à soulager les enfants malades en France et dans le monde, a accepté de s'engager à nos cotés pour que ce centre de medecine moleculaire, tourné entre autres vers les pathologies des enfants, prenne de vitesse les maladies et continue à relever les defis actuels.

INEM - Organigramme