A possible role for secreted ferritin in tissue iron distribution

Ferritin is known as a well-conserved iron detoxification and storage protein that is found in the cytosol of many prokaryotic and eukaryotic organisms. In insects and worms, ferritin has evolved into a classically secreted protein that transports iron systemically. Mammalian ferritins are found intracellularly in the cytosol, as well as in the nucleus, the endo-lysosomal compartment and the mitochondria. Extracellular ferritin is found in fluids such as serum and synovial and cerebrospinal fluids. We recently characterized the biophysical properties, secretion mechanism and cellular origin of mouse serum ferritin, which is actively secreted by a non-classical pathway involving lysosomal processing. Here, we review the data to support a hypothesis that intracellular and extracellular ferritin may play a role in intra- and intercellular redistribution of iron.