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

171 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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