MicroRNA-Mediated Regulation of Dp53 in the Drosophila Fat Body Contributes to Metabolic Adaptation to Nutrient Deprivation

Abstract

Multiple conserved mechanisms have evolved to sense nutritional conditions and to coordinate the corresponding metabolic changes of the whole organism. We unravel a role of Drosophila p53 (Dp53) in the fat body (FB), a functional analogue of vertebrate adipose and hepatic tissues, in metabolic adaptation to starvation. Under nutrient deprivation, FB-specific depletion of Dp53 accelerates the consumption of the main energy storages, and reduces the survival rates of adult flies. We show that Dp53 is regulated by the microRNA machinery in a nutrition-dependent manner and identify miR-305 as a major regulatory element. In well-fed animals, TOR signalling contributes to miR-305-mediated inhibition of Dp53. Nutrient deprivation reduces the levels of major elements of the miRNA machinery and leads to Dp53 de-repression. Our results reveal an organismal role of Dp53 in nutrient sensing and metabolic adaptation, and open up new avenues towards understanding the molecular mechanisms underlying p53 activation under nutrient deprivation.