NIP/DuoxA, originally cloned as a protein capable of Omega-3 Fish Oil binding to the cell fate determinant Numb in Drosophila, was recently identified as a modulator of reactive oxygen species (ROS) production in mammalian systems.Despite biochemical and cellular studies that link NIP/DuoxA to the generation of ROS through the dual oxidase (Duox) enzyme, the in vivo function of NIP/DuoxA has not been characterized to date.Here we report a genetic and functional characterization of nip in Drosophila melanogaster.We show that nip is essential for Drosophila development as nip null mutants die at the 1st larval instar.
Expression of UAS-nip, but not UAS-Duox, rescued the lethality.To understand the function of nip beyond the early larval stage, we generated GAL4 inducible UAS-RNAi transgenes.daG32-GAL4 driven, ubiquitous RNAi-mediated silencing of nip led to profound abnormality in pre-adult development, crinkled wing and markedly reduced lifespan Outdoor Dining Set at 29°C.Compared to wild type flies, da-GAL4 induced nip-RNAi transgenic flies exhibited significantly reduced ability to survive under oxidative stress and displayed impaired mitochondrial aconitase function.
Our work provides in vivo evidence for a critical role for nip in the development and oxidative stress response in Drosophila.