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

•Dp53 activity in the fat body confers organismal resistance to nutrient deprivation•Depletion of Dp53 accelerates consumption of major energy stores•Dp53 activity is regulated by nutrients and the miRNA machinery•TOR regulates Dp53 activity levels through miR-305

SummaryMultiple conserved mechanisms sense nutritional conditions and coordinate metabolic changes in the whole organism. We unravel a role for the Drosophila homolog of p53 (Dp53) in the fat body (FB; a functional analog of vertebrate adipose and hepatic tissues) in starvation adaptation. Under nutrient deprivation, FB-specific depletion of Dp53 accelerates consumption of major energy stores and reduces survival rates of adult flies. We show that Dp53 is regulated by the microRNA (miRNA) machinery and miR-305 in a nutrition-dependent manner. In well-fed animals, TOR signaling contributes to miR-305-mediated inhibition of Dp53. Nutrient deprivation reduces the levels of miRNA machinery components and leads to Dp53 derepression. Our results uncover an organism-wide role for Dp53 in nutrient sensing and metabolic adaptation and open up avenues toward understanding the molecular mechanisms underlying p53 activation under nutrient deprivation.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slide