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Identification of a mammalian mitochondrial porphyrin transporter

  • 작성자한진
  • 작성일2006-10-10 13:24:15
  • 조회수2603
  • 첨부파일첨부파일
Letter Nature advance online publication 27 September 2006 | doi:10.1038/nature05125; Received 25 April 2006; Accepted 25 July 2006; Published online 27 September 2006 Identification of a mammalian mitochondrial porphyrin transporter Partha C. Krishnamurthy1,5, Guoqing Du1,5, Yu Fukuda1,4, Daxi Sun1, Janardhan Sampath1, Kelly E. Mercer1, Junfeng Wang2, Beatriz Sosa-Pineda2, K. Gopal Murti3 and John D. Schuetz1 Top of pageThe movement of anionic porphyrins (for example, haem) across intracellular membranes is crucial to many biological processes, but their mitochondrial translocation and coordination with haem biosynthesis is not understood. Transport of porphyrins into isolated mitochondria is energy-dependent1, 2, 3, as expected for the movement of anions into a negatively charged environment. ATP-binding cassette transporters actively facilitate the transmembrane movement of substances. We found that the mitochondrial ATP-binding cassette transporter ABCB6 is upregulated (messenger RNA and protein in human and mouse cells) by elevation of cellular porphyrins and postulated that ABCB6 has a function in porphyrin transport. We also predicted that ABCB6 is functionally linked to haem biosynthesis, because its mRNA is found in both human bone marrow and CD71+ early erythroid cells (by database searching), and because our results show that ABCB6 is highly expressed in human fetal liver, and Abcb6 in mouse embryonic liver. Here we demonstrate that ABCB6 is uniquely located in the outer mitochondrial membrane and is required for mitochondrial porphyrin uptake. After ABCB6 is upregulated in response to increased intracellular porphyrin, mitochondrial porphyrin uptake activates de novo porphyrin biosynthesis. This process is blocked when the Abcb6 gene is silenced. Our results challenge previous assumptions about the intracellular movement of porphyrins and the factors controlling haem biosynthesis. Top of pageDepartment of Pharmaceutical Sciences and Department of Genetics and Tumor Cell Biology, and the Scientific Imaging Resource Center, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105-2794, USA University of Tennessee Health Sciences Center, Memphis, Tennessee 38103, USA *These authors contributed equally to this work Correspondence to: John D. Schuetz1 Correspondence and requests for materials should be addressed to J.D.S. (Email: john.schuetz@stjude.org).
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