Erebosis, a new cell death mechanism during homeostatic turnover of gut enterocytes

Abstract

Many adult tissues are composed of differentiated cells and stem cells, each working in a coordinated manner to maintain tissue homeostasis during physiological cell turnover. Old differentiated cells are believed to typically die by apoptosis. Here, we discovered a previously uncharacterized, new phenomenon, which we name erebosis based on the ancient Greek word erebos (“complete darkness”), in the gut enterocytes of adult Drosophila. Cells that undergo erebosis lose cytoskeleton, cell adhesion, organelles and fluorescent proteins, but accumulate Angiotensin-converting enzyme (Ance). Their nuclei become flat and occasionally difficult to detect. Erebotic cells do not have characteristic features of apoptosis, necrosis, or autophagic cell death. Inhibition of apoptosis prevents neither the gut cell turnover nor erebosis. We hypothesize that erebosis is a cell death mechanism for the enterocyte flux to mediate tissue homeostasis in the gut. It has been believed that gut enterocytes continuously die through apoptosis. However, this study shows that gut enterocytes die through a novel cell death mechanism, named erebosis. Erobotic cells lack the characteristic features of apoptotic, necrotic or autophagic cell death; instead they lose their cytoskeleton, cell adhesion and organelles, and their nuclei become flat and indistinct.