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

作者：Barrio Lara; Dekanty Andres; Milan Marco^*

来源：Cell Reports, 2014, 8(2): 527-540.

DOI：10.1016/j.celrep.2014.06.020

Multiple 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.

• 出版日期2014-7-24