Programmed cell death (PCD) is critical for multi-cellular organisms during development and in the maintenance of cellular homeostasis. Although most programmed cell death (PCD) during animal development occurs by caspase-dependent apoptosis, autophagy dependent cell death is also important in specific contexts. Previous studies in our laboratory have established that PCD of the Drosophila larval midgut tissue is dependent on autophagy instead of the apoptosis.
The ubiquitin-like conjugation system involving Atg3 Atg4 Atg5 Atg6 Atg7 and Atg8 is important for membrane formation in starvation-induced autophagy. We and others have previously shown that in the autophagy mediating PCD, most of these Atg proteins are not required. Instead, members of other ubiquitination pathways, such as uba1, are important for pro-death autophagy. Suggesting distinct autophagy programs are used. To disclose an unappreciated role for ubiquitination activation in pro-death autophagy, we have performed a genetical screen with the aid of RNAi lines targeting ubiquitin and ubiquitin-like protein modifiers. Novel regulators of autophagy including SIAH, lubel and PSC have been identified.