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Interorganellar association mediates the efficient transfer of iron from endosome to mitochondria
Author(s) -
Sheftel Alex D.,
Zhang Ansheng,
Brown Claire,
Shirihai Orian S.,
Ponka Prem
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1348-b
Subject(s) - endosome , ferrochelatase , cytosol , mitochondrion , endocytosis , heme , transferrin receptor , microbiology and biotechnology , transferrin , chemistry , ferritin , cytoplasm , mitochondrial matrix , protoporphyrin ix , biophysics , biochemistry , cell , biology , enzyme , photodynamic therapy , organic chemistry
Iron (Fe) is a transition metal whose physicochemical properties make it the focus of vital biological processes in virtually all living organisms. Paradoxically, the same characteristics that biochemistry exploits make Fe a potentially lethal substance. Differentiating erythroid cells acquire vast amounts of Fe at a breakneck rate. After cells acquire Fe via receptor‐mediated endocytosis, it is transferred from the endosome to the mitochondrial matrix where ferrochelatase catalyzes the insertion of the metal into protoporphyrin IX to form heme. Using both biochemical and microscopic strategies, we show that developing erythroid cells deliver the metal directly from endosome to mitochondrion, bypassing the cytosol. Reticulocytes whose cytosol was loaded with a membrane‐impermeant Fe chelator elicited no decrease in Fe incorporation into heme when Fe was delivered to the cells by the physiological chelate, transferrin (Tf). Additionally live‐cell imaging revealed a movement of Tf‐containing structures to mitochondria which was associated with an increase in mitochondrial iron. Using electron microscopy we observed an interorganellar association of a tubular, Tf‐containing network with mitochondria.