Direct interorganellar transfer of iron from endosome to mitochondrion

Blood - Tập 110 - Trang 125-132 - 2007
Alex D. Sheftel1, An-Sheng Zhang2, Claire Brown3, Orian S. Shirihai4, Prem Ponka1
1Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital and Department of Physiology, McGill University, Montréal, QC;
2Department of Cellular and Developmental Biology, Oregon Health & Science University, Portland, OR;
3Life Science Complex Imaging Facility, McGill University, Montreal, QC;
4Department of Pharmacology and Experimental Therapeutics, Tufts University, Boston, MA

Tóm tắt

Iron is a transition metal whose physicochemical 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.


Tài liệu tham khảo

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