Nuclear ferritin: A new role for ferritin in cell biology

Biochim Biophys Acta. 2010 Aug;1800(8):793-7. doi: 10.1016/j.bbagen.2010.03.017. Epub 2010 Mar 25.

Abstract

Background: Ferritin has been traditionally considered a cytoplasmic iron storage protein. However, several studies over the last two decades have reported the nuclear localization of ferritin, specifically H-ferritin, in developing neurons, hepatocytes, corneal epithelial cells, and some cancer cells. These observations encouraged a new perspective on ferritin beyond iron storage, such as a role in the regulation of iron accessibility to nuclear components, DNA protection from iron-induced oxidative damage, and transcriptional regulation.

Scope of review: This review will address the translocation and functional significance of nuclear ferritin in the context of human development and disease.

Major conclusions: The nuclear translocation of ferritin is a selective energy-dependent process that does not seem to require a consensus nuclear localization signal. It is still unclear what regulates the nuclear import/export of ferritin. Some reports have implicated the phosphorylation and O-glycosylation of the ferritin protein in nuclear transport; others suggested the existence of a specific nuclear chaperone for ferritin. The data argue strongly for nuclear ferritin as a factor in human development and disease. Ferritin can bind and protect DNA from oxidative damage. It also has the potential of playing a regulatory role in transcription.

General significance: Nuclear ferritin represents a novel new outlook on ferritin functionality beyond its classical role as an iron storage molecule.

Publication types

  • Review

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Cell Biology / trends
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • DNA Damage / genetics
  • DNA Damage / physiology
  • Ferritins / genetics
  • Ferritins / metabolism
  • Ferritins / physiology*
  • Humans
  • Iron / metabolism
  • Oxidative Stress / genetics
  • Oxidative Stress / physiology

Substances

  • Ferritins
  • Iron