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.