Autophagy and programmed cell death (PCD) are essential for animal development and for the maintenance of cell and tissue homeostasis. Autophagy is a conserved process that delivers components of the cytoplasm to lysosomes for degradation. Most PCD occurs by caspase-mediated apoptosis, with other mechanisms such as autophagy-dependent cell death, having crucial spatiotemporal restricted roles.

To study PCD during development we have been using Drosophila as a model. In our seminal findings we discovered that autophagy acts as a cell death mechanism required for the removal of a specific tissue during development, the larval midgut. Midgut PCD occurred normally in the absence of the apoptotic machinery, where as inhibition of autophagy blocked degradation. We found that hormonal cues together with growth arrest are prerequisite for autophagy-dependent midgut PCD. In our studies to understand the signalling pathways that regulate midgut removal we identified the TGF-β pathway.

As autophagy can act as either a cell survival or cell death mediator this raises the question of how autophagy specifically results in the demise of the cell. Our studies have shown that some components of the canonical autophagy pathway required for survival are dispensable for autophagy-dependent cell death. This suggests that there are unidentified components involved in autophagy-dependent PCD. We have been using proteomic and genetic approaches to identify tissue specific regulators of cell death verses cell survival autophagy. The findings from these studies will be discussed.