Fluid flow-induced shear stress controls the metabolism of proximal tubule kidney epithelial cells through primary cilium-dependent lipophagy and mitochondria biogenesis

Abstract

The kidney, similar to many other organs, has to face shear stress induced by biological fluids. How epithelial kidney cells respond to shear stress is poorly understood. Recently we showed in vitro and in vivo that proximal tubule epithelial cells use lipophagy to fuel mitochondria with fatty acids. Lipophagy is stimulated by a primary cilium-dependent signaling that converges at AMP kinase. AMP kinase is a central signaling hub to trigger lipophagy and also to stimulate mitochondrial biogenesis. These two pathways contribute to generate ATP needed to support energy-consuming cellular processes such as glucose reabsorption, gluconeogenesis. These findings demonstrate the role of the primary cilium and selective macroautophagy/autophagy to integrate shear stress and to sustain the execution of a specific cellular program.

Keywords: macroautophagy; metabolism; nephrology; oxidative phosphorylation.

Figure 1.

Shear stress and primary cilium-dependent autophagy are key regulators of proximal tubule epithelial cell metabolism and differentiation phenotype