An organismal role of Dp53 in metabolic adaptation to nutrient deprivation

*LARA BARRIO, *ANDRES DEKANTY, MARCO MILAN (*AUTHORS CONTRIBUTED EQUALLY)

San Diego

Conferencia; 55th Annual Drosophila Research Conference; 2014

Multiple conserved mechanisms have evolved to sense differences in nutrition and coordinate the corresponding metabolic changes of the whole organism. In the last few years, the tumour suppressor protein p53 has added to its repertoire of anti-tumoural activities the ability to mediate metabolic changes at the cellular level. Nevertheless, this function may contribute not only to tumour supression but also to non-cancer-associated functions of p53. Here we unravel a fundamental 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, depletion of Dp53 activity specifically in the FB, accelerates the consumption of the main energy storages and reduces the survival rates of adult flies. Energy storage in FB cells is well known to be modulated by the combined action of insulin-like peptides and adipokinetic hormone. However, we suggested that Dp53 has an impact on energy balance independently on the regulation of fasting hormones and identified a cell-autonomous role of Dp53 in regulating energy metabolism. Moreover, we characterized the molecular mechanism by which Dp53 activity is modulated by nutritional stress. We present evidence that Dp53 is regulated in FB cells in a cell-autonomous manner by the levels of nutrients (amino acids specifically) and the TOR signaling pathway. Our results reveal an organismal role of Dp53 in nutrient sensing and metabolic adaptation in front of a nutrient stress and open up new avenues towards understanding the molecular mechanisms underlying the activation of p53 under nutrient deprivation.