Ferritin Overview
- Ferritin heavy chain (FTH) (molecular weight of 21 kDa) is encoded by a gene located on chromosome 11q.
- Ferritin light chains (FTL) (molecular weight of 15.7 kDa) is encoded by a gene located on chromosome 19q.
- A total of 24 ferritin heavy and light chains assemble into a shell, creating a spherical protein that possesses a large cavity (protein cage). This iron-free protein is called apoferritin (molecular weight of about 450 kDa) (the iron-containing form is termed holoferritin or simply ferritin). The ratio of heavy to light chains is highly variable between cell types and tissues. The ratio is high in kidney, brain and heart, and low in liver and spleen.
- Ferrous iron (Fe2+) enters the apoferritin shell through iron channels or pores. FTH has ferroxidase activity that rapidly oxidizes Fe2+ into the ferric form (Fe3+).
- A small amount of ferritin is secreted into the extracellular space, and may be found in the serum. Serum ferritin is comprised almost exclusively of light chains and is iron poor.
- Ferritin expression is regulated by iron at a posttranscriptional level (both heavy and light chains) and by cytokines at a transcriptional level (primarily H chains).
- Ferritin is processed in lysosomes via several pathways:
- Secretion of ferritin into extracellular space and plasma (serum ferritin) via an NCOA4-independent mechanisms
- Iron release for use in the cell via NCOA4-dependent mechanisms
- Conversion/breakdown into hemosiderin, another storage form of intracellular iron.