Cellular uptake of human H-ferritin loaded with 50 or 350 iron ions results in significant cytotoxicity on HeLa cells at submicromolar concentrations. Conversely, Horse Spleen Ferritin, that can be considered a model of L-cages, as it contains only about 10% of H subunits, even when loaded with 1000 iron ions, is toxic only at >1 order of magnitude higher protein concentrations. We propose here that the different cytotoxicity of the two ferritin cages originates from the presence in H-ferritin of a pool of non-biomineralized iron ions bound at the ferroxidase catalytic sites of H-ferritin subunits. This iron pool is readily released during the endosomal-mediated H-ferritin internalization.

Cancer cell death induced by ferritins and the peculiar role of their labile iron pool / Cutrin, Juan Carlos; Alberti, Diego; Bernacchioni, Caterina; Ciambellotti, Silvia; Turano, Paola; Luchinat, Claudio; Crich, Simonetta Geninatti*; Aime, Silvio. - In: ONCOTARGET. - ISSN 1949-2553. - ELETTRONICO. - 9:(2018), pp. 27974-27984. [10.18632/oncotarget.25416]

Cancer cell death induced by ferritins and the peculiar role of their labile iron pool

Bernacchioni, Caterina
Methodology
;
Ciambellotti, Silvia
Methodology
;
Turano, Paola
Writing – Review & Editing
;
Luchinat, Claudio
Writing – Review & Editing
;
2018

Abstract

Cellular uptake of human H-ferritin loaded with 50 or 350 iron ions results in significant cytotoxicity on HeLa cells at submicromolar concentrations. Conversely, Horse Spleen Ferritin, that can be considered a model of L-cages, as it contains only about 10% of H subunits, even when loaded with 1000 iron ions, is toxic only at >1 order of magnitude higher protein concentrations. We propose here that the different cytotoxicity of the two ferritin cages originates from the presence in H-ferritin of a pool of non-biomineralized iron ions bound at the ferroxidase catalytic sites of H-ferritin subunits. This iron pool is readily released during the endosomal-mediated H-ferritin internalization.
2018
9
27974
27984
Cutrin, Juan Carlos; Alberti, Diego; Bernacchioni, Caterina; Ciambellotti, Silvia; Turano, Paola; Luchinat, Claudio; Crich, Simonetta Geninatti*; Aime...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1139531
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