Blood Journal
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Brief report
Ferrochelatase forms an oligomeric complex with mitoferrin-1 and Abcb10 for erythroid heme biosynthesis

  1. Wen Chen1,
  2. Harry A. Dailey2, and
  3. Barry H. Paw1
  1. 1Department of Medicine, Hematology Division, Brigham & Women's Hospital; Department of Medicine, Hematology-Oncology Division, Children's Hospital Boston; and Harvard Medical School, Boston, MA; and
  2. 2Departments of Microbiology, Biochemistry & Molecular Biology, and Biomedical and Health Sciences Institute, University of Georgia, Athens

Abstract

In erythroid cells, ferrous iron is imported into the mitochondrion by mitoferrin-1 (Mfrn1). Previously, we showed that Mfrn1 interacts with Abcb10 to enhance mitochondrial iron importation. Herein we have derived stable Friend mouse erythroleukemia (MEL) cell clones expressing either Mfrn1-FLAG or Abcb10-FLAG and by affinity purification and mass spectrometry have identified ferrochelatase (Fech) as an interacting protein for both Mfrn1 and Abcb10. Fech is the terminal heme synthesis enzyme to catalyze the insertion of the imported iron into protoporphyrin IX to produce heme. The Mfrn1-Fech and Abcb10-Fech interactions were confirmed by immunoprecipitation/Western blot analysis with endogenous proteins in MEL cells and heterologous proteins expressed in HEK293 cells. Moreover, Fech protein is induced in parallel with Mfrn1 and Abcb10 during MEL cell erythroid differentiation. Our findings imply that Fech forms an oligomeric complex with Mfrn1 and Abcb10 to synergistically integrate mitochondrial iron importation and use for heme biosynthesis.

  • Submitted December 15, 2009.
  • Accepted April 20, 2009.
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