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Blood, 1 January 2005, Vol. 105, No. 1, pp. 368-375. Prepublished online as a Blood First Edition Paper on August 26, 2004; DOI 10.1182/blood-2004-06-2226. This Article Full Text (PDF) All Versions of this Article: 2004-06-2226v1 105/1/368    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhang, A.-S. Articles by Ponka, P. Search for Related Content PubMed PubMed Citation Articles by Zhang, A.-S. Articles by Ponka, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 14, 2004 Accepted August 13, 2004 Intracellular kinetics of iron in reticulocytes: evidence for endosome involvement in iron targeting to mitochondria An-Sheng Zhang, Alex D Sheftel, and Prem Ponka* Department of Cellular and Developmental Biology, Oregon Health Sciences University, Portland, OR, USA Department of Physiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada * Corresponding author; email: prem.ponka{at}mcgill.ca. In erythroid cells the vast majority of iron (Fe) released from endosomes must cross both the outer and the inner mitochondrial membranes to reach ferrochelatase that inserts Fe into protoporphyrin IX. In the present study, we developed a method whereby a cohort of 59Fe-transferrin (Tf) laden endosomal vesicles were generated, from which we could evaluate the transfer of 59Fe into mitochondria. Iron chelators, dipyridyl or salicylaldehyde isonicotinoyl hydrazone (SIH) were able to bind the 59Fe when they were present during a 37°C incubation, however addition of these agents only during lysis at 4°C chelated virtually no 59Fe. Bafilomycin A1 (which prevents endosome acidification) and succinylacetone (an inhibitor of 5-aminolevulinate dehydratase) prevented endosomal 59Fe incorporation into heme. Importantly, both the myosin light chain kinase inhibitor wortmannin and the calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalene- sulfonamide (W-7), caused significant inhibition of 59Fe incorporation from 59Fe-Tf-labeled endosomes into heme, suggesting that myosin is required for Tf-vesicle movement. Our results reaffirm the astonishing efficiency of Tf-derived Fe utilization in hemoglobin (Hb)-producing cells and demonstrate that very little of this Fe is present in a chelatable pool. Collectively, these results are congruent with our hypothesis that a transient endosome-mitochondrion interaction mediates iron transfer between these organelles. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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