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  • The EMBO Journal (2006) 25, 5396 - 5404
  • doi:10.1038/sj.emboj.7601409

Published online: 2 November 2006

Ferroportin-mediated mobilization of ferritin iron precedes ferritin degradation by the proteasome

Ivana De Domenico1,a, Michael B Vaughn1,a, Liangtao Li1, Dustin Bagley1, Giovanni Musci2, Diane M Ward1 and Jerry Kaplan1

  1. Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah, USA
  2. Dipartimento di Scienze e Tecnologie Agro-alimentari, Ambientali e Microbiologiche, Univerisity of Molise, Campobasso, Italy

Correspondence to:

Jerry Kaplan, Department of Pathology, University of Utah School of Medicine, 50 North Medical Drive, Salt Lake City, UT 84132, USA. Tel.: +1 801 581 7427; Fax: +1 801 581 6001; E-mail: jerry.kaplan@path.utah.edu

aThese authors contributed equally to the work

Received 23 August 2006; Accepted 5 October 2006

Ferritin is a cytosolic molecule comprised of subunits that self-assemble into a nanocage capable of containing up to 4500 iron atoms. Iron stored within ferritin can be mobilized for use within cells or exported from cells. Expression of ferroportin (Fpn) results in export of cytosolic iron and ferritin degradation. Fpn-mediated iron loss from ferritin occurs in the cytosol and precedes ferritin degradation by the proteasome. Depletion of ferritin iron induces the monoubiquitination of ferritin subunits. Ubiquitination is not required for iron release but is required for disassembly of ferritin nanocages, which is followed by degradation of ferritin by the proteasome. Specific mammalian machinery is not required to extract iron from ferritin. Iron can be removed from ferritin when ferritin is expressed in Saccharomyces cerevisiae, which does not have endogenous ferritin. Expressed ferritin is monoubiquitinated and degraded by the proteasome. Exposure of ubiquitination defective mammalian cells to the iron chelator desferrioxamine leads to degradation of ferritin in the lysosome, which can be prevented by inhibitors of autophagy. Thus, ferritin degradation can occur through two different mechanisms.

  • Keywords:

    • ferritin,
    • iron,
    • proteasome,
    • ubiquitin,
    • yeast