PI3K, stress and autophagy


Boukhalfa A, Nascimbeni AC, Ramel D, Dupont N, Hirsch E, Gayral S, Laffargue M, Codogno P, Morel E.

Link to the original article

Year of publication



Nat Commun.


Primary cilium-dependent autophagy is induced by fluid flow in polarized epithelial cells. A major physiological outcome of this autophagic pathway is the control of epithelial cell size. Shear stress induced by the liquid flow promotes PI3P synthesis at the primary cilium, and this lipid is required both for ciliogenesis and for autophagy initiation. We reported here that PI3P is generated by PI3KC2α, but not by PI3KC3 (VPS34), during flow associated primary cilium-dependent autophagy, in a ULK1 independent manner. Along the same line Beclin1, a partner of PI3KC3 in starvation induced autophagy, is not recruited at the primary cilium under shear stress. Thus ciliated epithelial cells mobilizes different PI3-Kinases, i.e., PI3KC2α or PI3KC3 to produce PI3P in order to initiate autophagy depending on the stimuli (shear stress or starvation). This illustrates the complex autophagic machinery mobilized regarding the kind of stress that epithelial cells have to face.

Graphical abstract

PI3KC2α-dependent and VPS34-independent generation of PI3P controls primary cilium-mediated autophagy in response to shear stress