Fat Body p53 Regulates Systemic Insulin Signaling and Autophagy under Nutrient Stress via Drosophila Upd2 Repression

INGARAMO MC; DEKANTY A

Congreso; 61 Annual Drosophila Research Conference; 2021

Genetic Society of America

The tumor suppressor p53 regulates multiple metabolic pathways at thecellular level. However, its role in the context of a whole animalresponse to metabolic stress is poorly understood. Using Drosophila,we show that AMPK-dependent Dmp53 activation is critical for sensingnutrient stress, maintaining metabolic homeostasis and extendingorganismal survival. Under both nutrient deprivation and high-sugardiet, Dmp53 activation in the fat body repress expression of theDrosophila Leptin analog, Unpaired-2 (Upd2), which remotely controlsDilp2 secretion in insulin producing cells. In straved Dmp53-depleted animals, elevated Upd2 expressionin adipose cells and subsequent activation of Upd2 receptor Domelessin the brain result in sustainedDilp2 circulating levels, activation of insulin/TOR signaling andimpaired autophagy induction throughout the entire body, thereforereducing survival rates upon nutrient deprivation. Our resultsdemonstrate an essential role for AMPK-Dmp53 axis in nutrient stressresponses and expand the concept that adipose tissue acts as a sensingorgan that orchestrate systemic adaptation to nutrient status.