A non-lytic membrane permeabilization program drives epithelial cell turnover in vivo

A central dilemma of epithelial cell turnover is eliminating and replacing cells while simultaneously preserving tissue architecture and barrier function. Conventionally, apoptotic or non-apoptotic cell extrusion has been implicated in the intestinal epithelial turnover. Here, we identify a non-lytic membrane permeabilization program that drives physiological enterocyte turnover in vivo . In the Drosophila intestine, enterocytes undergo erebosis, a non-apoptotic form of cell death characterized by depletion of cytoplasmic proteins. We discover that this process is mediated by transient plasma membrane pores with estimated diameters of 16–50 nm, permitting extracellular protein influx and loss of cytoplasmic contents. The pore-forming protein Ninjurin A (NijA) accumulates as puncta during erebosis, and is necessary and sufficient for driving this process. NijA-mediated transient permeabilization preserves the membrane framework of dying cells, enabling their replacement without disrupting epithelial barrier architecture.