A possible role for secreted ferritin in tissue iron distribution

Abstract

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.

Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency

“…The release/secretion and uptake of ferritin from both hepatocytes and macrophages, which may be controlled by extracellular stimuli, has been proposed before, 10,50,51 as has the notion that ferritin acts both as an iron carrier and iron storage protein. 52,53 Combined with the HCV-mediated increase in hepcidin, these data indicate that the virus may use both hepcidin-dependent and independent pathways to manipulate iron homeostasis and set up a macrophagic reservoir that would permit viral transmission, at least in vitro. Attesting to that notion was the ability of macrophages taken from HCVinfected co-cultures to "de novo" infect na€ ıve hepatoma cells.…”

Extremely High Ferritinemia Associated with Haemophagocytic Lympho Histiocytosis (HLH)

“…Within the cytosol it stores iron in a non soluble non toxic form and so protecting the cell. In the circulation it acts as delivery mechanism and its serum level reflect total iron body store [1]. It can be elevated in wide range of conditions such as malignancy, infection, septic shock, inflammation and chronic iron overload syndrome.…”

Apoferritin: protein nanocarrier for targeted delivery

“…Although ferritin is considered to represent cytoplasmic iron storage, novel functions for ferritin have recently been discovered, including ability to deliver iron into the brain across the blood brain barrier via clathrin mediated endocytosis, using recently described receptors [transferrin receptor 1 (TfR1), T cell immunoglobulin and mucin domain-containing protein-2 (TIM2), scavenger receptor class A, member 5 (SCARA5)] [39,40]. Ferritin can also be an important factor in angiogenesis, where the binding of ferritin to the antiangiogenic cleaved form of kininogen abrogates its anti-angiogenic function, thus mediating pro-angiogenic processes [41].…”