Human mitochondrial ferritin expressed in HeLa cells incorporates iron and affects cellular iron metabolism

Barbara Corsi, Anna Cozzi, Paolo Arosio, Jim Drysdale, Paolo Santambrogio, Alessandro Campanella, Giorgio Biasiotto, Alberto Albertini, Sonia Levi

Research output: Contribution to journalArticle

Abstract

Mitochondrial ferritin (MtF) is a newly identified ferritin encoded by an intronless gene on chromosome 5q23.1. The mature recombinant MtF has a ferroxidase center and binds iron in vitro similarly to H-ferritin. To explore the structural and functional aspects of MtF, we expressed the following forms in HeLa cells: the MtF precursor (∼28 kDa), a mutant MtF precursor with a mutated ferroxidase center, a truncated MtF lacking the ∼6-kDa mitochondrial leader sequence, and a chimeric H-ferritin with this leader sequence. The experiments show that all constructs with the leader sequence were processed into ∼22-kDa subunits that assembled into multimeric shells electrophoretically distinct from the cytosolic ferritins. Mature MtF was found in the matrix of mitochondria, where it is a homopolymer. The wild type MtF and the mitochondrially targeted H-ferritin both incorporated the 55Fe label in vivo. The mutant MtF with an inactivated ferroxidase center did not take up iron, nor did the truncated MtF expressed transiently in cytoplasm. Increased levels of MtF both in transient and in stable transfectants resulted in a greater retention of iron as MtF in mitochondria, a decrease in the levels of cytosolic ferritins, and up-regulation of transferrin receptor. Neither effect occurred with the mutant MtF with the inactivated ferroxidase center. Our results indicate that exogenous iron is as available to mitochondrial ferritin as it is to cytosolic ferritins and that the level of MtF expression may have profound consequences for cellular iron homeostasis.

Original languageEnglish
Pages (from-to)22430-22437
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number25
DOIs
Publication statusPublished - Jun 21 2002

ASJC Scopus subject areas

  • Biochemistry

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