| ferritin, light polypeptide | |
|---|---|
| Structure of the ferritin complex.[1] | |
| Identifiers | |
| Symbol | FTL |
| Entrez | 2512 |
| HUGO | 3999 |
| OMIM | 134790 |
| RefSeq | NM_000146 |
| UniProt | P02792 |
| Other data | |
| Locus | Chr. 19 q13.3–13.4 |
| ferritin, heavy polypeptide 1 | |
|---|---|
| Identifiers | |
| Symbol | FTH1 |
| Alt. symbols | FTHL6 |
| Entrez | 2495 |
| HUGO | 3976 |
| OMIM | 134770 |
| RefSeq | NM_002032 |
| UniProt | P02794 |
| Other data | |
| Locus | Chr. 11 q13 |
| ferritin mitochondrial | |
|---|---|
| Crystallographic structure of mitochondrial ferritin.[2] | |
| Identifiers | |
| Symbol | FTMT |
| Entrez | 94033 |
| HUGO | 17345 |
| OMIM | 608847 |
| RefSeq | NM_177478 |
| UniProt | Q8N4E7 |
| Other data | |
| Locus | Chr. 5 q23.1 |
Ferritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including algae, bacteria and higher plants, and animals. In humans, it acts as a buffer against iron deficiency and iron overload.[3]
Ferritin is a globular protein complex consisting of 24 protein subunits and is the primary intracellular iron-storage protein in both prokaryotes and eukaryotes, keeping iron in a soluble and non-toxic form. Ferritin that is not combined with iron is called apoferritin.
Contents |
Ferritin is a protein of 450 kDa consisting of 24 subunits that is present in every cell type.[4] In vertebrates, these subunits are both the light (L) and the heavy (H) type with an apparent molecular weight of 19 kDA or 21 kDA respectively; their sequences are about 50% homologous.[4] Amphibians have an additional ("M") type of ferritin;[5] the single ferritin of plants and bacteria most closely resembles the vertebrate H-type.[5] Two types have been recovered in the gastropod Lymnaea, the somatic ferritin being distinct from the yolk ferritin (see below).[5] An additional subunit resembling Lymnaea soma ferritin is associated with shell formation in the pearl oyster.[6] Two types are present in the parasite Schistosoma, one in males, the other in females.[5] All the aforementioned ferritins are almost similar, in terms of their primary sequence, with the vertebrate H-type.[5] In E. coli, a 20% similarity to human H-ferritin is recovered.[5] Inside the ferritin shell, iron ions form crystallites together with phosphate and hydroxide ions. The resulting particle is similar to the mineral ferrihydrite. Each ferritin complex can store about 4500 iron (Fe3+) ions.[4][5]
Some ferritin complexes in vertebrates are hetero-oligomers of two highly-related gene products with slightly different physiological properties. The ratio of the two homologous proteins in the complex depends on the relative expression levels of the two genes.
Mitochondrial ferritin was recently identified as a protein precursor, and is classified as a metal-binding protein that is located within the mitochondria.[7] After the protein is taken up by the mitochondria it can be processed into a mature protein and assemble functional ferritin shells. Its structure was determined at 1.70 angstroms through the use of X-ray diffraction and contains 182 residues. It is 67% helical. The Ramachandran plot [8] shows that the structure of mitochondrial ferritin is mainly alpha helical with a low prevalence of beta sheets. Unlike other human ferritin, it appears to have no introns in its genetic code.
In human ferritin, introns are present between the 34/5th, 82/3rd, and 14/5th amino acid residues; in addition, one to two hundred untranslated bases grace either end of the combined exons.[4] The Tyrosine residue at amino acid position 27 is thought to be associated with biomineralization.[9]
Ferritin serves to store iron in a non-toxic form, to deposit it in a safe form, and to transport it to areas where it is required.[10] The function and structure of the expressed ferritin protein varies in different cell types. This is controlled primarily by how much mRNA is translated, and how stable the mRNA is. mRNA concentration is further tweaked by changes to how it is stored and how efficiently it is transcribed.[4] The presence of iron itself is a major trigger for the production of ferritin,[4] with some exceptions (such as the yolk ferritin of the gastropod Lymnaea, which lacks an iron-responsive unit).[5]
Free iron is toxic to cells as it acts as a catalyst in the formation of free radicals from reactive oxygen species via the Fenton Reaction.[11] Hence vertebrates use an elaborate set of protective mechanisms to bind iron in various tissue compartments. Within cells, iron is stored in a protein complex as ferritin or hemosiderin. Apoferritin binds to free ferrous iron and stores it in the ferric state. As ferritin accumulates within cells of the reticuloendothelial system, protein aggregates are formed as hemosiderin. Iron in ferritin or hemosiderin can be extracted for release by the RE cells although hemosiderin is less readily available. Under steady state conditions, the serum ferritin level correlates with total body iron stores; thus, the serum ferritin FR5Rl is the most convenient laboratory test to estimate iron stores.
Because iron is an important mineral in mineralization, ferritin is employed in the shells of organisms such as molluscs to control the concentration and distribution of iron, thus sculpting shell morphology and colouration.[12][13] It also plays a role in the haemolymph of the polyplacophora where it serves to rapidly transport iron to the mineralizing radula.[14]
The heavy chain of Ferritin also possesses ferroxidase activity, this involves the conversion of iron from the ferrous (Fe2+) to ferric (Fe 3+) forms. This limits the deleterious reaction which occurs between ferrous iron and hydrogen peroxide known as the Fenton reaction which produces the highly damaging hydroxyl radical.
Ferritin concentrations increase drastically in the presence of an infection or cancer; this is necessary to counter the infective agent's attempt to bind iron from the host's tissue.[15] The inflammatory response may cause ferritin to migrate from the plasma to within cells, in order to deny iron to the infective agent.[15]
The concentration of ferritin has been shown to increase in response to stresses such as anoxia;[16] this implies that it is an acute phase protein.[17]
Mitochondrial ferritin has many roles pertaining to molecular function. It participates in ferroxidase activity, binding, iron ion binding, oxidoreductase activity, ferric iron binding, metal ion binding as well as transition metal binding. Within the realm of biological processes it participates in oxidation-reduction, iron ion transport across membranes and cellular iron ion homeostasis.
In some snails, the protein component of the egg yolk is primarily ferritin;[18] this is a different ferritin, with a different genetic sequence, than the somatic ferritin. It is produced in the midgut glands and secreted into the haemolymph, whence it is transported to the eggs.[18]
Ferritin is also used in materials science as a precursor in making iron nanoparticles for carbon nanotube growth by chemical vapor deposition.
In vertebrates, ferritin is usually found within cells, although it is also present in smaller quantities in the plasma.[15]
Serum ferritin levels are measured in medical laboratories as part of the iron studies workup for anemia and for restless legs syndrome. The ferritin levels measured usually have a direct correlation with the total amount of iron stored in the body. However, ferritin levels may be artificially high in cases of anemia of chronic disease where ferritin is elevated in its capacity as an acute phase protein and not as a marker for iron overload.
A normal ferritin blood level, referred to as the reference interval is determined by many testing laboratories. The ranges for ferritin can vary between laboratories but are usually between 30–400 ng/mL (=μg/L) for males, and 15–200 ng/mL (=μg/L) for females.
If the ferritin level is low, there is a risk for lack of iron, which could lead to anemia. Low ferritin levels (<50 ng/mL) have, however, been associated with the symptoms of restless legs syndrome, even in the absence of anemia and sickness.[19]
In the setting of anemia, serum ferritin is the most specific lab test for iron deficiency anemia.[20] However it is less sensitive, since its levels are increased in the blood by infection, or any type of chronic inflammation, and these conditions may convert what would otherwise be a low level of ferritin from lack of iron, into a value in the normal range. For this reason, low ferritin levels carry more information than those in the normal range.
Low ferritin may also indicate hypothyroidism, vitamin C deficiency or celiac disease.
If ferritin is high, there is iron in excess or else there is an acute inflammatory reaction in which ferritin is mobilized without iron excess. For example, ferritins may be high in infection without signalling body iron overload.
Ferritin is also used as a marker for iron overload disorders, such as hemochromatosis, hemosiderosis. Adult-onset Still's disease, porphyria and Hemophagocytic lymphohistiocytosis are diseases in which the ferritin level may be abnormally raised.
As ferritin is also an acute-phase reactant, it is often elevated in the course of disease. A normal C-reactive protein can be used to exclude elevated ferritin caused by acute phase reactions.
Ferritin can be elevated during periods of acute malnourishment.[21]
Cavities formed by ferritin and mini-ferritins (Dps) proteins have been successfully used as the reaction chamber for the fabrication of metal nanoparticles (NPs).[22][23][24][25] Protein shells served as a template to restrain particle growth and as a coating to prevent coagulation/aggregation between NPs. Using various sizes of protein shells, various sizes of NPs can be easily synthesized for chemical, physical and bio-medical applications
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