Role of Dp53 in metabolic homeostasis and autophagy under nutrient stress

DEKANTY, ANDRES; INGARAMO, MARIA CLARA

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

SAIB

The ability of an organism to adapt to nutritional stress is crucial forits survival. We have previously shown that the transcription factorDp53 plays a central role in metabolic remodeling in Drosophila. Depletionof Dp53 activity specifically in the adipose tissue acceleratesthe consumption of main energy stores, reduces the levels of sugarsin the animal, and compromises organismal survival upon fasting. Inthis work, we aim to investigate in more detail the role of Dp53 in responseto nutrient deprivation. By using a combination of transgenicreporter lines and fluorescent dyes we found that Dp53 is requiredfor the induction of autophagy, a conserved catabolic process whichis central in the nutrient stress response. This function of Dp53 appearsto 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 appearsto be a systemic function rather than through cell-autonomous mechanisms. Insulin-like peptides (dIlps) regulate physiological andmetabolic responses to nutrients in Drosophila and, consistently, weobserved differences in dIlps expression levels and insulin signalingwhen Dp53 activity was compromised in the fatbody. From theseresults, we propose that Dp53 is required in the fatbody to remotelymodulate insulin secretion and/or production in the brain thereforeproviding mechanisms for rapid adaptation to starvation conditions.