Corneal epithelial nuclear ferritin: developmental regulation of ferritin and its nuclear transporter ferritoid.

The corneal epithelium is exposed to reactive oxygen species that are potentially deleterious to nuclear DNA. However, our previous studies show that corneal epithelial cells have a novel, developmentally regulated mechanism for protection from such damage that involves having the iron-sequestering molecule, ferritin, in the nucleus. Nuclear localization of ferritin is achieved through the action of a tissue-specific nuclear transporter, ferritoid, which is itself a ferritin family member. Here, we show that during development ferritoid appears before ferritin. At this time, ferritoid is cytoplasmic, suggesting that its nuclear transport function requires an interaction with ferritin. To examine the developmental regulation of these two interacting components, cultured corneas were treated with the iron chelator deferoxamine. The results show that, while iron-mediated translational regulation is involved in the synthesis of both molecules, ferritoid is also transcriptionally regulated, demonstrating that these family members--whose functions depend upon one another--are regulated differently.