ROLE OF DP53 IN METABOLIC HOMEOSTASIS AND AUTOPHAGY UNDER NUTRIENT STRESS

INGARAMO, MARIA CLARA; DEKANTY, ANDRES

Buenos aires

Congreso; LIII REUNIÓN ANUAL DE LASOCIEDAD ARGENTINA DE INVESTIGACIÓN BIOQUÍMICA Y BIOLOGÍA MOLECULAR; 2017

The ability of an organism to adapt to nutritional stress is crucial for its survival. We have previously shown that the transcription factor Dp53 plays a central role in metabolic remodeling in Drosophila. De-pletion of Dp53 activity specifically in the adipose tissue accelerates the consumption of main energy stores, reduces the levels of sugars in the animal, and compromises organismal survival upon fasting. In this work, we aim to investigate in more detail the role of Dp53 in response to nutrient deprivation. By using a combination of transgenic reporter lines and fluorescent dyes we found that Dp53 is required for the induction of autophagy, a conserved catabolic process which is central in the nutrient stress response. This function of Dp53 appears to be tissue specific as depletion of Dp53 protein levels and/or activity in the fatbody strongly reduced starvation-induced autophagy. Interestingly, the role of Dp53 in modulating autophagy appears to be a systemic function rather than through cell-autonomousmechanisms. Insulin-like peptides (dIlps) regulate physiological and metabolic responses to nutrients in Drosophila and, consistently, we observed differences in dIlps expression levels and insulin signaling when Dp53 activity was compromised in the fatbody. From these results, we propose that Dp53 is required in the fatbody to remotely modulate insulin secretion and/or production in the brain therefore providing mechanisms for rapid adaptation to starvation conditions.