foxo is required for resistance to amino acid starvation in Drosophila

The ability of an organism to alter its metabolism, growth, and reproductive capacity in response to fluctuations in food availability has likely been an important factor in the course Of evolution. The insulin signalling pathway is an evolutionarily conserved mechanism used by metazoan animals to sense and respond to changes in nutrient intake. During conditions of starvation the level of circulating insulin is low. Under conditions of low insulin, the foxo family of transcription factors are activated. Studies in Drosophila Suggest that Drosophila foxo may alter the transcriptional profile of cells to allow for maximum survival of the fly during starvation. We have tested this ability in transgenic flies containing a luciferase reporter gene under the control of foxo response elements. We show that foxo activity is increased during amino acid starvation and reduced in the presence of amino acids. In addition, we find that loss of function of foxo leads to reduced survival under conditions of amino acid starvation in both larvae and adult flies. These data provide direct evidence that foxo is activated during amino acid starvation and is critical for optimal survival under these conditions.