FTH1

FTH1, or ferritin heavy chain 1, is a gene that encodes one of the core subunits of ferritin, the intracellular iron-storage protein. The ferritin complex sequesters iron in a non-toxic, soluble form to prevent iron-catalyzed formation of reactive oxygen species.

Ferritin is a 24-subunit nanocage composed of heavy chain (FTH1) and light chain (FTL) subunits. The heavy chain carries ferroxidase activity that converts Fe2+ to Fe3+, enabling iron to be stored as ferric oxides within the core. The relative ratio of heavy to light chains influences the rates of iron oxidation and mineralization. A single ferritin complex can store up to about 4,500 iron atoms.

In humans, FTH1 is expressed widely and is regulated by cellular iron levels. Iron regulatory proteins bind to iron-responsive elements in the FTH1 mRNA to modulate translation in response to iron availability. Serum ferritin, which largely reflects intracellular ferritin, is used clinically as a marker of iron stores and inflammation; it can be elevated in infection, malignancy, and chronic disease.

Dysregulation of ferritin heavy chain expression or ferritin storage function has been linked to iron-related disorders and neurodegenerative diseases. In cancer, ferritin expression frequently changes and may influence cellular iron handling and oxidative stress. Additional context includes the existence of mitochondrially targeted ferritin (FTMT) and the iron-regulatory network that controls ferritin turnover through ferritinophagy mediated by NCOA4.