Redox reactions associated with iron release from mammalian ferritin

The early redox events involved in iron reduction and mobilization in mammalian ferritin have been investigated by several techniques. Sedimentation velocity measurements of ferritin samples with altered core sizes, prepared by partial reduction and Fe2+ chelation, suggest two different events occur during iron loss from the ferritin core. Reductive optical titrations confirm this biphasic behavior by showing that the first 20-30% of core reduction has different optical properties than the latter 70-80%. Proton uptake during initial core reduction is near zero, but as the percent core reduction increases, the proton uptake (H+/e) values increase to 2 H+/e (2 H+/Fe3+ reduced) as core reduction approaches 1 e/Fe3+. Coulometric reduction of ferritin by mediators of different redox potential and different cross-sectional areas show a two-phase sigmoidal reaction pattern in which initial core reduction occurs at a slower rate than later core reduction. The above experiments were all conducted in the absence of iron chelators so that the observed results were all attributed to core reduction rather than the combined effects of core reduction accompanied by Fe2+ chelation. The coulometric reduction of ferritin by various mediators shows a correlation more with reduction potential than with molecular cross-sectional area. The role of the ferritin channels in core reduction is considered in terms of the reported results.