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.

Cells need to sense stresses to initiate the execution of the dormant cell death program. Since the discovery of the first BH3‐only protein Bad, BH3‐only proteins have been recognized as indispensable stress sensors that induce apoptosis. BH3‐only proteins have so far not been identified in Drosophila despite their importance in other organisms. Here, we identify the first Drosophila BH3‐only protein and name it sayonara. Sayonara induces apoptosis in a BH3 motif‐dependent manner and interacts genetically and biochemically with the BCL‐2 homologous proteins, Buffy and Debcl. There is a positive feedback loop between Sayonara‐mediated caspase activation and autophagy. The BH3 motif of sayonara phylogenetically appeared at the time of the ancestral gene duplication that led to the formation of Buffy and Debcl in the dipteran lineage. To our knowledge, this is the first identification of a bona fide BH3‐only protein in Drosophila, thus providing a unique example of how cell death mechanisms can evolve both through time and across taxa.

Graphical Abstract Highlights d Octopaminergic signaling regulates postsynaptic Dlp levels during starvation d dlp is required for starvation-induced synaptic growth and locomotor behavior d Dlp regulates GluRIIA-mediated non-canonical BMP signaling d This BMP signaling regulates starvation-induced behavioral and synaptic plasticities SUMMARYUnder food deprivation conditions, Drosophila larvae exhibit increases in locomotor speed and synaptic bouton numbers at neuromuscular junctions (NMJs). Octopamine, the invertebrate counterpart of noradrenaline, plays critical roles in this process; however, the underlying mechanisms remain unclear. We show here that a glypican (Dlp) negatively regulates type I synaptic bouton formation, postsynaptic expression of GluRIIA, and larval locomotor speed. Starvation-induced octopaminergic signaling decreases Dlp expression, leading to increases in synapse formation and locomotion. Dlp is expressed by postsynaptic muscle cells and suppresses the non-canonical BMP pathway, which is composed of the presynaptic BMP receptor Wit and postsynaptic GluRIIA-containing ionotropic glutamate receptor. We find that during starvation, decreases in Dlp increase non-canonical BMP signaling, leading to increases in GluRIIA expression, type I bouton number, and locomotor speed. Our results demonstrate that octopamine controls starvation-induced neural plasticity by regulating Dlp and provides insights into how proteoglycans can influence behavioral and synaptic plasticity.