title: Oxido-reduction is not the only mechanism allowing ions to traverse the ferritin protein shell.
abstract: BACKGROUND
  Most models for ferritin iron release are based on reduction and chelation of iron. However, newer models showing direct Fe(III) chelation from ferritin have been proposed. Fe(III) chelation reactions are facilitated by gated pores that regulate the opening and closing of the channels.
  
  
  METHODS
  Results suggest that iron core reduction releases hydroxide and phosphate ions that exit the ferritin interior to compensate for the negative charge of the incoming electrons. Additionally, chloride ions are pumped into ferritin during the reduction process as part of a charge balance reaction. The mechanism of anion import or export is not known but is a natural process because phosphate is a native component of the iron mineral core and non-native anions have been incorporated into ferritin in vitro. Anion transfer across the ferritin protein shell conflicts with spin probe studies showing that anions are not easily incorporated into ferritin. To accommodate both of these observations, ferritin must possess a mechanism that selects specific anions for transport into or out of ferritin. Recently, a gated pore mechanism to open the 3-fold channels was proposed and might explain how anions and chelators can penetrate the protein shell for binding or for direct chelation of iron.
  
  
  CONCLUSIONS
  These proposed mechanisms are used to evaluate three in vivo iron release models based on (1) equilibrium between ferritin iron and cytosolic iron, (2) iron release by degradation of ferritin in the lysosome, and (3) metallo-chaperone mediated iron release from ferritin.
authors.affiliation: Department of Chemistry and Biochemistry, C-100 Benson Building, Brigham Young University, Provo, UT 84602, USA. rwatt@chem.byu.edu
authors.forename: Richard K
authors.initials: RK
authors.lastname: Watt
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hilton
authors.forename: D Matthew
authors.initials: DM
authors.lastname: Graff
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D020134:Catalytic Domain; D005293:Ferritins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007477:Ions / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D010084:Oxidation-Reduction; D017434:Protein Structure, Tertiary / Q000502:physiology; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism / Q000502:physiology
chemical_list: D007477:Ions; D021122:Protein Subunits; D005293:Ferritins; D007501:Iron