Identification of iron-loaded ferritin as an essential mitogen for cell proliferation and postembryonic development...

Animal cells require extrinsic cues for growth, proliferation and survival. The propagation of Drosophila imaginal disc cells in vitro, for example, requires the supplementation of fly extract, the composition of which remains largely undefined. Here I report the biochemical purification of iron-loaded ferritin as an active ingredient of fly extract that is required for promoting the growth of clone 8 imaginal disc cells. Consistent with an essential role for iron-loaded ferritin in cultured cells, overexpression of ferritin or addition of iron in a nutrient-poor diet increases animal viability and body weight, promotes cell proliferation, and shortens the duration of postembryonic development. Conversely, overexpression of dominant-negative ferritin or addition of iron chelator causes the opposite effects. Ferritin mutant flies arrest development at the first-instar larval stage with a severe starvation phenotype reminiscent of that seen in starved larvae. I conclude that iron-loaded ferritin acts as an essential mitogen for cell proliferation and postembryonic development in Drosophila by maintaining iron homeostasis and antagonizing starvation response.