Chemically and biologically harmless versus harmful ferritin/ copper-metallothionein couples

© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. The simultaneous measurement of the decrease of available FeIIions and the increase of available FeIIIions allowed the analysis of the ferroxidase activity of two distinct apoferritins. Although recombinant human apoferritin (HuFtH) rapidly oxidizes FeIIto FeIII, this iron is not properly stored in the ferritin cavity, as otherwise occurs in horse-spleen H/L-apoferritin (HsFt; H = heavy subunit, L= light subunit). Iron storage in these apoferritins was also studied in the presence of two copper-loaded mammalian metallothioneins (MT2 and MT3), a scenario that occurs in different brain-cell types. For HuFtH, unstored FeIIIions trigger the oxidation of Cu-MT2 with concomitant Cu I release. In contrast, there is no reaction with Cu-MT2 in the case of HsFt. Similarly, Cu-MT3 does not react during either HuFtH or HsFt iron reconstitution. Significantly, the combination of ferritin and metallothionein isoforms reported in glia and neuronal cells are precisely those combinations that avoid a harmful release of FeIIand CuI ions.