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.

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