The FTH1 gene, or Ferritin Heavy Chain 1, provides instructions for making the ferritin heavy chain protein. This protein is a component of ferritin, a spherical structure composed of 24 subunits, which can be a mix of heavy (FTH1) and light (FTL) chains. This complex is the main way cells store iron. The FTH1 gene is located on chromosome 11 in humans.
FTH1’s Role in Iron Management
The primary function of the FTH1 protein is its involvement in cellular iron storage and detoxification. As part of the ferritin complex, FTH1 helps encapsulate and safely store excess iron, preventing its toxic effects within the cell. Iron in its ferrous form (Fe2+) can generate harmful reactive oxygen species if left unbound. The FTH1 subunit possesses ferroxidase activity, meaning it can convert ferrous iron (Fe2+) into ferric iron (Fe3+).
This oxidation is a step that allows iron to be deposited as ferric hydroxides inside the ferritin protein’s central cavity. This process is important for maintaining iron balance, also known as iron homeostasis, within the body’s cells. Different ratios of heavy and light ferritin chains can affect how quickly iron is taken up and released in various tissues. FTH1 also participates in delivering iron to cells.
FTH1 and Health Conditions
Disruptions in the normal function of the FTH1 gene or its protein are linked to several health conditions, particularly those involving iron dysregulation. One notable association is with Hemochromatosis type 5, a disorder characterized by iron overload. In this condition, mutations in the FTH1 gene can lead to an accumulation of iron in various tissues.
FTH1 dysfunction also plays a role in neurodegenerative diseases, where abnormal iron accumulation in the brain is often observed. For example, neuroferritinopathy, a type of neurodegeneration with brain iron accumulation (NBIA), has been linked to heterozygous variants in FTH1. These variants can lead to elevated ferritin protein levels and increased susceptibility to iron accumulation, particularly in brain regions like the basal ganglia.
Beyond Iron: Emerging Roles of FTH1
Beyond its established role in iron metabolism, FTH1 is being investigated for its involvement in other cellular processes. It participates in the cellular response to oxidative stress, acting as a protector against damage caused by reactive molecules. FTH1 is also a component in ferritinophagy, which mobilizes stored iron. This process involves the NCOA4 protein binding to FTH1, directing the iron-loaded ferritin to lysosomes for degradation.
FTH1’s role in immune modulation and inflammation is also gaining attention. Research suggests it can influence the immune response, and its expression can be altered in inflammatory conditions. FTH1 has also been implicated in certain cancers, where its expression levels can vary and potentially impact tumor growth and progression.