Drosophila dMRP4 regulates responsiveness to O2 deprivation and development under hypoxia

ness to O2 deprivation and development under hypoxia. Physiol Genomics 29: 260–266, 2007. First published February 6, 2007; doi:10.1152/physiolgenomics.00166.2006.—For most vertebrates, oxygen is a prerequisite for survival. Although we have previously shown that Drosophila melanogaster is hypoxia tolerant, how this species senses O2 deprivation and how it survives oxygen-limiting conditions are as yet poorly understood. We began to address this question by testing for anoxic responsiveness in Drosophila adult flies following overexpression of existing EP lines. In this screen, we identified Drosophila CG14709 gene as a homolog of the human multidrug resistance protein 4 (MRP4/ABCC4) that is tightly regu-lated to oxygen. Ubiquitous expression of dMRP4 in adult flies resulted in increased sensitivity to anoxia as they had longer recovery time from anoxic stupor. When exposed to 4 % oxygen chronically (throughout its lifespan), constitutive expression of dMRP4 in larva