IRON METABOLISM IN MOSQUITOS

Iron is an essential mineral for all species. We are studying iron metabolism in the disease vector, Aedes aegypti. Ferritin and the iron regulatory protein 1 (IRP1) are important proteins of vertebrate iron metabolism. Ferritin is required for intracellular iron storage, and IRP1 is an important translational regulatory control factor for ferritin expression. Our work indicates that both proteins are also present in mosquitos. Our central hypothesis is that changes in the expression of ferritin and in IRP1 activity contribute to the ability of the females to adapt to the iron load of a blood meal. Our specific aims are to study the structure and function of Ae. aegypti IRP1 (aIRP1), to determine whether the aIRP1 regulates translation of the Ae. aegypti ferritin subunits, and to evaluate the effect of iron availability on the in vivo expression of ferritin and IRP1, and on aIRP1 activity in mosquito cells. We will accomplish these aims by studying the in vitro formation of an iron sulfur cluster in the IRP1, aconitase activity of aIRP1, aIRP1 control of in vitro translation of ferritin messages, and the expression of ferritin, IRP1 and IRP1/IRE binding activity in Ae. aegypti Aag2 cells in response to iron deprivation and excess. Our long term goals are: (1) to study the effects of an iron load on the expression of iron-binding proteins in mosquitos; (2) to study changes in the expression of these proteins in mosquitos during development; and (3) to evaluate the potential effects of nitric oxide and oxidants on the synthesis and function of these proteins in mosquito cells. This work will provide information that could apply to the areas of (1) vector intracellular iron metabolism, (2) vector/parasite relationships, (3) vector defense mechanisms and (4) mosquito development.