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.

摘要

与许多其他器官类似，肾脏必须承受由生物体液引起的剪切应力。上皮肾细胞如何对剪切应力作出反应还知之甚少。最近我们在体外和体内表明，近端小管上皮细胞使用脂肪吞噬作用为线粒体提供脂肪酸。脂肪自噬受到聚集于 AMP 激酶的初级纤毛依赖性信号的刺激。AMP 激酶是一个中央信号枢纽，可触发脂肪吞噬并刺激线粒体生物发生。这两种途径有助于产生支持能量消耗细胞过程所需的 ATP，如葡萄糖重吸收、糖异生。这些发现证明了初级纤毛和选择性巨自噬/自噬在整合剪切应力和维持特定细胞程序执行方面的作用。