• Paola Ruzzenenti, Michela Asperti, Stefania Mitola, Elisabetta Crescini, Federica Maccarinelli, Magdalena Gryzik, Maria Regoni, Dario Finazzi, Paolo Arosio, and Maura Poli.
• Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, Brescia, Italy.
• Biochim. Biophys. Acta. 2015 Jun 1;1850(6):1267-73.

BackgroundThree functional ferritin genes have been identified so far in mammals, and they encode the cytosolic Heavy (FTH) and Light chain (FTL) and the mitochondrial ferritin. The expression of a transcript by a fourth ferritin-like gene (Ferritin-Heavy-Polypeptide-Like-17, FTHL17) on the X chromosome was reported in mouse spermatogonia and in early embryonic cells.MethodsThe intronless human FTHL17 gene encodes a protein with 64% identity to human FTH with substitution of key residues of the ferroxidase center. The gene was cloned into vectors for expression in Escherichia coli and mammalian cells, linked to a flag-tag.ResultsThe recombinant FTHL17 from E. coli purified as an assembled 24-mer ferritin devoid of ferroxidase activity and with a reduced physical stability. When transiently expressed in mammalian cells the flag-FTHL17 assembled in ferritin shells that showed reduced stability to denaturants compared with flag H and L ferritins. Immunocytochemistry with anti-flag antibody decorated the nuclei of flag-FTHL17 transfected COS cells, but not those of the cells transfected with flag-FTH or flag-FTL.ConclusionsWe concluded that FTHL17 encodes a ferritin-like protein without ferroxidase activity. Its restricted embryonic expression and partial nuclear localization suggest that this novel ferritin type may have functions other than iron storage.General SignificanceThe work confirms the presence of a fourth functional human ferritin gene with properties distinct from the canonical cytosolic ones.Copyright © 2015 Elsevier B.V. All rights reserved.

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