Activation of autophagy during cell death requires the engulfment receptor Draper.

Abstract

Autophagy degrades cytoplasmic components that are required for cell survival in response to starvation1. Autophagy has also been associated with cell death, but it is unclear what may distinguish autophagy during cell survival and death. Drosophila salivary glands undergo programmed cell death that requires autophagy genes2, and engulfment of salivary gland cells by phagocytes does not appear to occur3. Here we show that Draper (Drpr), the Drosophila orthologue of the C. elegans engulfment receptor CED-1, is required for autophagy during cell death. Null mutations in drpr, as well as salivary gland-specific knockdown of drpr, inhibits salivary gland degradation. drpr knockdown prevents the induction of autophagy in dying salivary glands, and Atg1 expression in drpr mutants suppresses the failure in salivary gland degradation. Surprisingly, drpr is cell-autonomously required for autophagy induction in dying salivary gland cells, while drpr knockdown does not prevent starvation-induced autophagy in the fatbody which is associated with survival. In addition, components of the conserved engulfment pathway are required for clearance of salivary glands. This is the first example of an engulfment factor that is autonomously required for self-clearance. Furthermore, Drpr is the first factor that distinguishes autophagy that is associated with cell death from cell survival.