Figure 7

Iron-induced ferritin aggregation and oxidative stress in HF. The mutant FTL polypeptide acts as a dominant negative mutant, leading to a failure of ferritin in its iron storage function and an increase in the levels of intracellular (ic) iron, resulting in the release of the IRP proteins from the ferritin IRE and degradation of TfR1 mRNA, generating a positive feed-back loop that leads to over-production of ferritin polypeptides. The C-termini of the mutant FTL polypeptides may extend above the spherical shell allowing them to crosslink with other ferritin molecules through iron bridging, promoting iron-mediated aggregation of ferritin. Free iron leads to the generation of ROS and oxidative stress. Ferritin aggregates and oxidative stress may lead to neurodegeneration in HF.