Reductive mobilisation of ferritin iron

Area of Science:

• Biochemistry
• Biomineralization
• Protein Chemistry

Background:

• Ferritin is the primary intracellular iron-storage protein.
• Understanding iron mobilization from ferritin is crucial for iron metabolism and related diseases.
• Previous studies have explored iron release mechanisms, but detailed kinetic differences remain to be elucidated.

Purpose of the Study:

• To investigate the reductive mobilization of iron from ferritin.
• To compare the kinetic characteristics of iron release induced by different reducing agents.
• To elucidate the mechanisms underlying iron release, focusing on pH dependence and surface interactions.

Main Methods:

• Kinetic analysis of iron release using dithionite, thioglycollate, and dihydroriboflavin 5'-phosphate (FMNH2).
• Investigation of pH dependence on iron release rates.
• Characterization of interactions between reducing agents/products and the ferritin iron core.

Main Results:

• Distinct kinetic profiles for iron release were observed with dithionite, thioglycollate, and FMNH2.
• Dithionite-mediated iron release showed significant pH dependence, being 100 times faster at pH 4 than pH 7.
• Experimental data supported mechanisms involving specific interactions of reactants or products with the ferritin core's iron(III) hydroxide, including surface complex formation.

Conclusions:

• The reductive mobilization of iron from ferritin is mediated by distinct pathways depending on the reducing agent.
• Surface complex formation plays a critical role in iron release, as evidenced by reactions with dithionite, thioglycollate, and various thiols.
• The findings suggest that interactions at the ferritin core surface, rather than hindered shell penetration, predominantly govern iron mobilization.