title: Iron release from ferritin by flavin nucleotides.
abstract: BACKGROUND
  Extensive in-vitro studies have focused on elucidating the mechanism of iron uptake and mineral core formation in ferritin. However, despite a plethora of studies attempting to characterize iron release under different experimental conditions, the in-vivo mobilization of iron from ferritin remains poorly understood. Several iron-reductive mobilization pathways have been proposed including, among others, flavin mononucleotides, ascorbate, glutathione, dithionite, and polyphenols. Here, we investigate the kinetics of iron release from ferritin by reduced flavin nucleotide, FMNH2, and discuss the physiological significance of this process in-vivo.
  
  
  METHODS
  Iron release from horse spleen ferritin and recombinant human heteropolymer ferritin was followed by the change in optical density of the Fe(II)-bipyridine complex using a Cary 50 Bio UV-Vis spectrophotometer. Oxygen consumption curves were followed on a MI 730 Clark oxygen microelectrode.
  
  
  RESULTS
  The reductive mobilization of iron from ferritin by the nonenzymatic FMN/NAD(P)H system is extremely slow in the presence of oxygen and might involve superoxide radicals, but not FMNH2. Under anaerobic conditions, a very rapid phase of iron mobilization by FMNH2 was observed.
  
  
  CONCLUSIONS
  Under normoxic conditions, FMNH2 alone might not be a physiologically significant contributor to iron release from ferritin.
  
  
  CONCLUSIONS
  There is no consensus on which iron release pathway is predominantly responsible for iron mobilization from ferritin under cellular conditions. While reduced flavin mononucleotide (FMNH2) is one likely candidate for in-vivo ferritin iron removal, its significance is confounded by the rapid oxidation of the latter by molecular oxygen.
authors.affiliation: Department of Chemistry & Biomolecular Science, Clarkson University, Potsdam, NY, USA. amelman@clarkson.edu
authors.forename: Galina
authors.initials: G
authors.lastname: Melman
authors.forename: Fadi
authors.initials: F
authors.lastname: Bou-Abdallah
authors.forename: Eleanor
authors.initials: E
authors.lastname: Vane
authors.forename: Poli
authors.initials: P
authors.lastname: Maura
authors.forename: Paolo
authors.initials: P
authors.lastname: Arosio
authors.forename: Artem
authors.initials: A
authors.lastname: Melman
mesh_terms: D000818:Animals; D005293:Ferritins / Q000378:metabolism*; D005486:Flavin Mononucleotide / Q000378:metabolism*; D006736:Horses; D006801:Humans; D007501:Iron / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
chemical_list: D009243:NAD; D005486:Flavin Mononucleotide; D005293:Ferritins; D007501:Iron
keywords: FMN/NAD(P)H; Ferritin; Iron core; Iron release; Oxygen consumption; Reductive mobilization