Genome-wide analyses of steroid- and radiation- triggered programmed cell death in Drosophila

Apoptosis and autophagy are two forms of programmed cell death that play important roles in the removal of unneeded and abnormal cells during animal development [1, 2]. While these two forms of programmed cell death are morphologically distinct, recent studies indicate that apoptotic and autophagic cell death utilize some common regulatory mechanisms [3-5]. To identify genes that are associated with apoptotic and autophagic cell death, we monitored changes in gene transcription by using microarrays representing nearly the entire Drosophila genome. Analyses of steroid-triggered autophagic cell death identified 932 gene transcripts that changed 5-fold or greater in RNA level. In contrast, radiation-activated apoptosis resulted in 34 gene transcripts that exhibited a similar magnitude of change. Analyses of these data enabled us to identify genes that are common and unique to steroid- and radiation-induced cell death. Mutants that prevent autophagic cell death exhibit altered levels of gene transcription, including genes encoding caspases, non-caspase proteases, and proteins that are similar to yeast autophagy proteins. This study also identifies numerous novel genes as candidate cell death regulators and suggests new links between apoptosis and autophagic cell death.