title: MicroRNA-mediated regulation of Dp53 in the Drosophila fat body contributes to metabolic adaptation to nutrient deprivation.
abstract: 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.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri i Reixac, 10, 08028 Barcelona, Spain.
authors.forename: Lara
authors.initials: L
authors.lastname: Barrio
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri i Reixac, 10, 08028 Barcelona, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Dekanty
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri i Reixac, 10, 08028 Barcelona, Spain; Institucio Catalana de Recerca i Estudis Avançats (ICREA), 08028 Barcelona, Spain. Electronic address: marco.milan@irbbarcelona.org.
authors.forename: Marco
authors.initials: M
authors.lastname: Milán
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D005216:Fat Body / Q000378:metabolism*; D005508:Food Deprivation; D035683:MicroRNAs / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C000594015:MIRN305 microRNA, Drosophila; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; C474203:p53 protein, Drosophila; D058570:TOR Serine-Threonine Kinases