Blood, 1 August 2001, Vol. 98, No. 3, pp. 503-504
Ferreting out the dynamics of ferritin expression
Ferritin is a remarkable molecule. A shell-like
megapolymer of similar 20-kd light (L) and 21-kd heavy (H) subunits, it
mediates a phase transition of soluble iron to solid ferric oxide,
incorporating up to 2000 metal atoms into its mineral core. All living
organisms exploit some form of this versatile molecule, using ferritin
as an intracellular iron-storage depot. In mammals, small amounts of
iron-poor ferritin escape from cells to circulate in the blood. Although the origin of serum ferritin is uncertain, it is widely considered to be a good clinical indicator of body iron stores.
Last year, Ferreira and colleagues made the important observation that
H and L subunits must have nonredundant functions, because mice lacking
H ferritin die early in gestation (Ferreira et al, J Biol Chem.
2000;275:3021-3024). Presumably, this is because H ferritin uniquely
possesses a ferroxidase activity that is necessary for iron
assimilation. In this issue (page 525), they extend their findings,
showing that animals with only one functional H ferritin gene have half
the normal levels of H ferritin but make up the difference by increased
expression of L ferritin.
These results are intriguing for 3 reasons. First, they suggest that
the L-to-H stoichiometry of isoferritins is less important than
previously suspected, because the mutant mice have no evidence of
abnormal iron homeostasis. Second, they indicate that regulation of
ferritin gene expression is complex. Mechanisms of transcriptional and
translational regulation have been studied in detail, but no existing
information readily explains the dynamic relationship between H and L
ferritin production in mice lacking one H ferritin gene. Finally, they
suggest a new etiology for isolated hyperferritinemia in otherwise
normal human patients.
Nancy C. Andrews
Howard Hughes Medical Institute; Children's Hospital Boston
