title: Ferrochelatase forms an oligomeric complex with mitoferrin-1 and Abcb10 for erythroid heme biosynthesis.
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.
authors.affiliation: Department of Medicine, Hematology Division, Brigham & Women's Hospital, 1 Blackfan Circle, Boston, MA 02115, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Harry A
authors.initials: HA
authors.lastname: Dailey
authors.forename: Barry H
authors.initials: BH
authors.lastname: Paw
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002478:Cells, Cultured; D041905:Erythroid Cells / Q000378:metabolism*; D005294:Ferrochelatase / Q000378:metabolism*; D006418:Heme / Q000096:biosynthesis*; D006801:Humans; D007501:Iron / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D055503:Protein Multimerization
chemical_list: D018528:ATP-Binding Cassette Transporters; C410734:Abcb10 protein, mouse; D026901:Membrane Transport Proteins; C509051:mitoferrin protein, mouse; D006418:Heme; D007501:Iron; D005294:Ferrochelatase