Direct interorganellar transfer of iron from endosome to mitochondrion

Alex D. Sheftel, An-Sheng Zhang, Claire Brown, Orian S. Shirihai, Prem Ponka

Research output: Contribution to journalArticle

170 Citations (Scopus)

Abstract

Iron is a transition metal whose physico-chemical properties make it the focus of vital biologic processes in virtually all living organisms. Among numerous roles, iron is essential for oxygen transport, cellular respiration, and DNA synthesis. Paradoxically, the same characteristics that biochemistry exploits make iron a potentially lethal substance. In the presence of oxygen, ferrous iron (Fe2+) will catalyze the production of toxic hydroxyl radicals from hydrogen peroxide. In addition, Fe3+ is virtually insoluble at physiologic pH. To protect tissues from deleterious effects of Fe, mammalian physiology has evolved specialized mechanisms for extracellular, intercellular, and intracellular iron handling. Here we show that developing erythroid cells, which are taking up vast amounts of Fe, deliver the metal directly from transferrin-containing endosomes to mitochondria (the site of heme biosynthesis), bypassing the oxygen-rich cytosol. Besides describing a new means of intracellular transport, our finding is important for developing therapies for patients with iron loading disorders.

Original languageEnglish (US)
Pages (from-to)125-132
Number of pages8
JournalBlood
Volume110
Issue number1
DOIs
StatePublished - Jul 1 2007

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Mitochondria
Endosomes
Iron
Oxygen
Metals
Cell Respiration
Erythroid Cells
Biochemistry
Poisons
Biosynthesis
Physiology
Transferrin
Heme
Hydroxyl Radical
Cytosol
Chemical properties
Hydrogen Peroxide
Transition metals
Tissue
DNA

ASJC Scopus subject areas

  • Hematology

Cite this

Direct interorganellar transfer of iron from endosome to mitochondrion. / Sheftel, Alex D.; Zhang, An-Sheng; Brown, Claire; Shirihai, Orian S.; Ponka, Prem.

In: Blood, Vol. 110, No. 1, 01.07.2007, p. 125-132.

Research output: Contribution to journalArticle

Sheftel, AD, Zhang, A-S, Brown, C, Shirihai, OS & Ponka, P 2007, 'Direct interorganellar transfer of iron from endosome to mitochondrion', Blood, vol. 110, no. 1, pp. 125-132. https://doi.org/10.1182/blood-2007-01-068148
Sheftel, Alex D. ; Zhang, An-Sheng ; Brown, Claire ; Shirihai, Orian S. ; Ponka, Prem. / Direct interorganellar transfer of iron from endosome to mitochondrion. In: Blood. 2007 ; Vol. 110, No. 1. pp. 125-132.
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