THE TRANSLATION INHIBITOR 4EBP IS REQUIRED FOR ADAPTATION TO HYPOXIA IN DROSOPHILA

ACEVEDO JM; SORIANELLO E; PEREZ PERRI J; MELANI M; KATZ MJ; VALKO A; WAPPNER P

Córdoba

Congreso; LII Reunión Anual de SAIB; 2016

SAIB

4EBP (eIF4E-binding protein is an inhibitor of cap-dependent mRNA translation whose activity is regulated by intracellular pathways that respond to energy availability. The transcription factor HIF mediates adaptation to hypoxia through mechanisms that reduce metabolism and oxygen consumption. The aim of this work is to determine if 4EBP is required for fly adaptation to hypoxia in vivo. We found that 4EBP transcription is strongly induced in hypoxia in embryos, larvae and adult flies. Transcriptional induction depends on the transcription factors FOXO and HIF. Drosophila 4EBP mutants are viable and fertile in normoxia but fail to survive in hypoxia. In adult flies lipids are equally consumed in wild type or 4EBP mutant flies. While oogenesis is arrested at early stages in wild type flies, in 4EBP mutants it proceeds to post-vitelogenic stages,provoking an energy imbalance that ultimately leads to lethality. We conclude that 4EBP is a central regulator of energy balance essential for adaptation to hypoxia in vivo.