Transferrin 1 Functions in Iron Trafficking and Genetically Interacts with Ferritin in Drosophila melanogaster

Iron metabolism is an essential process that when dysregulated causes disease. Mammalian serum transferrin (TF) plays a primary role in delivering iron to cells. To improve our understanding of the conservation of iron metabolism between species, we investigate here the function of the TF homolog in Drosophila melanogaster, transferrin 1 (Tsf1). Tsf1 knockdown results in iron accumulation in the gut and iron deficiency in the fat body (which is analogous to the mammalian liver). Fat body-derived Tsf1 localizes to the gut surface, suggesting that Tsf1 functions in trafficking iron between the gut and the fat body, similar to TF in mammals. Moreover, Tsf1 knockdown strongly suppresses the phenotypic effects of ferritin (Fer1HCH) RNAi, an established iron trafficker in Drosophila. We propose that Tsf1 and ferritin compete for iron in the Drosophila intestine and demonstrate the value of using Drosophila for investigating iron trafficking and the evolution of systemic iron regulation.