Role of ferritin in the control of the labile iron pool in murine erythroleukemia cells

Virginie Picard, Silvina Epsztejn, Paolo Santambrogio, Z. Ioav Cabantchik, Carole Beaumont

Research output: Contribution to journalArticlepeer-review

Abstract

In vitro studies have shown that ferritin iron incorporation is mediated by a ferroxidase activity associated with ferritin H subunits (H-Ft) and a nucleation center associated with ferritin L subunits (L-Ft). To assess the role played by the ferritin subunits in regulating intracellular iron distribution, we transfected mouse erythroleukemia cells with the H-Ft subunit gene mutated in the iron-responsive element. Stable transfectants displayed high H-Ft levels and reduced endogenous L-Ft levels, resulting in a marked change in the H:L subunit ratio from 1:1 in control cells to as high as 20:1 in some transfected clones. The effects of H-Ft overexpression on the labile iron pool were determined in intact cells by a novel method based on the fluorescent metallosensor calcein. H-Ft overexpression resulted in a significant reduction in the iron pool, from 1.3 μM in control cells to 0.56 μM in H-Ft transfectants, and in higher buffering capacity following iron loads. A fraction of the H-Ftassociated iron was labile, available to cell- permeant, but not cell-impermeant, chelators. The results of this study provide the first in vivo direct demonstration of the capacity of H-Ft to sequester cell iron and to regulate the levels of the labile iron pool.

Original languageEnglish
Pages (from-to)15382-15386
Number of pages5
JournalJournal of Biological Chemistry
Volume273
Issue number25
DOIs
Publication statusPublished - Jun 19 1998

ASJC Scopus subject areas

  • Biochemistry

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