Ferritin: the protein nanocage and iron biomineral in health and in disease

Inorg Chem. 2013 Nov 4;52(21):12223-33. doi: 10.1021/ic400484n. Epub 2013 Oct 8.


At the center of iron and oxidant metabolism is the ferritin superfamily: protein cages with Fe(2+) ion channels and two catalytic Fe/O redox centers that initiate the formation of caged Fe2O3·H2O. Ferritin nanominerals, initiated within the protein cage, grow inside the cage cavity (5 or 8 nm in diameter). Ferritins contribute to normal iron flow, maintenance of iron concentrates for iron cofactor syntheses, sequestration of iron from invading pathogens, oxidant protection, oxidative stress recovery, and, in diseases where iron accumulates excessively, iron chelation strategies. In eukaryotic ferritins, biomineral order/crystallinity is influenced by nucleation channels between active sites and the mineral growth cavity. Animal ferritin cages contain, uniquely, mixtures of catalytically active (H) and inactive (L) polypeptide subunits with varied rates of Fe(2+)/O2 catalysis and mineral crystallinity. The relatively low mineral order in liver ferritin, for example, coincides with a high percentage of L subunits and, thus, a low percentage of catalytic sites and nucleation channels. Low mineral order facilitates rapid iron turnover and the physiological role of liver ferritin as a general iron source for other tissues. Here, current concepts of ferritin structure/function/genetic regulation are discussed and related to possible therapeutic targets such as mini-ferritin/Dps protein active sites (selective pathogen inhibition in infection), nanocage pores (iron chelation in therapeutic hypertransfusion), mRNA noncoding, IRE riboregulator (normalizing the ferritin iron content after therapeutic hypertransfusion), and protein nanovessels to deliver medicinal or sensor cargo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anemia / drug therapy
  • Animals
  • Catalytic Domain
  • Drug Delivery Systems / methods*
  • Ferritins / chemistry*
  • Ferritins / genetics
  • Ferritins / metabolism*
  • Hemosiderin / metabolism
  • Humans
  • Iron Overload / drug therapy
  • Molecular Targeted Therapy / methods*
  • Nanostructures / administration & dosage
  • RNA, Messenger
  • Transfusion Reaction


  • RNA, Messenger
  • Ferritins
  • Hemosiderin