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.