title: Endoplasmic reticulum anchored heme-oxygenase 1 faces the cytosol.
abstract: Heme-oxygenase 1 is an endoplasmic reticulum-anchored enzyme that breaks down heme into iron, carbon monoxide and biliverdin. Heme is a hydrophobic co-factor in many proteins, including hemoglobin. Free heme is highly cytotoxic and, therefore, both heme synthesis and breakdown are tightly regulated. During turnover of heme proteins, heme is released in the phago-lysosomal compartment or the cytosol. The subcellular location of the heme-oxygenase 1 active site has not been clarified. Using constructs of heme-oxygenase 1 with fluorescent proteins, and the endogenous heme-oxygenase 1 in two variations of protease protection assays, we determined that heme-oxygenase 1 is membrane-bound and faces the cytosol in non-activated macrophages in vivo. These findings imply that in quiescent macrophages, heme breakdown products are generated in the cytosol. This facilitates iron recycling to ferroportin for iron export and to ferritin for iron storage.
authors.affiliation: Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Yehonatan
authors.initials: Y
authors.lastname: Gottlieb
authors.forename: Marianna
authors.initials: M
authors.lastname: Truman
authors.forename: Lyora A
authors.initials: LA
authors.lastname: Cohen
authors.forename: Yael
authors.initials: Y
authors.lastname: Leichtmann-Bardoogo
authors.forename: Esther G
authors.initials: EG
authors.lastname: Meyron-Holtz
mesh_terms: D000818:Animals; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004789:Enzyme Activation; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport
chemical_list: D006418:Heme; D051547:Heme Oxygenase-1