Activation of autophagy during cell death requires the engulfment receptor Draper

Abstract

Autophagy, the process by which a cell digests its own components in the lysosomes, is an ancient and well-conserved pathway that acts as a survival response to starvation but has also been associated with cell death. In this study, McPhee et al. identify the first factor that regulates autophagy during cell death, but not during cell survival. They find that in Drosophila, the engulfment receptor Draper is a critical regulator of autophagy during cell death of Drosophila salivary glands but is not required for starvation-induced autophagy during fat body cell survival. This is the first example of an engulfment factor that is autonomously required for self-clearance. 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 how this is distinguished from autophagy during cell survival. 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 melanogaster orthologue of the Caenorhabditis elegans engulfment receptor CED-1, is required for autophagy during cell death. Null mutations in, and salivary gland-specific knockdown of, drpr inhibit salivary gland degradation. Knockdown of drpr prevents the induction of autophagy in dying salivary glands, and expression of the Atg1 autophagy regulator in drpr mutants suppresses the failure in degradation of salivary glands. Surprisingly, drpr is required in the same dying salivary gland cells in which it regulates autophagy induction, but drpr knockdown does not prevent starvation-induced autophagy in the fat body, which is associated with survival. In addition, components of the conserved engulfment pathway are required for clearance of dying salivary glands. To our knowledge, this is the first example of an engulfment factor that is required for self-clearance of cells. Further, Drpr is the first factor that distinguishes autophagy that is associated with cell death from autophagy associated with cell survival.