title: Heme and erythropoieis: more than a structural role.
abstract: Erythropoiesis is the biological process that consumes the highest amount of body iron for heme synthesis. Heme synthesis in erythroid cells is finely coordinated with that of alpha (α) and beta (β)-globin, resulting in the production of hemoglobin, a tetramer of 2α- and 2β-globin chains, and heme as the prosthetic group. Heme is not only the structural component of hemoglobin, but it plays multiple regulatory roles during the differentiation of erythroid precursors since it controls its own synthesis and regulates the expression of several erythroid-specific genes. Heme is synthesized in developing erythroid progenitors by the stage of proerythroblast, through a series of eight enzymatic reactions divided between mitochondria and cytosol. Defects of heme synthesis in the erythroid lineage result in sideroblastic anemias, characterized by microcytic anemia associated to mitochondrial iron overload, or in erythropoietic porphyrias, characterized by porphyrin deposition in erythroid cells. Here, we focus on the heme biosynthetic pathway and on human erythroid disorders due to defective heme synthesis. The regulatory role of heme during erythroid differentiation is discussed as well as the heme-mediated regulatory mechanisms that allow the orchestration of the adaptive cell response to heme deficiency.
authors.affiliation: Department of Molecular Biotechnology and Health Sciences and Molecular Biotechnology Center, University of Torino, Italy.
authors.forename: Deborah
authors.initials: D
authors.lastname: Chiabrando
authors.affiliation: Department of Molecular Biotechnology and Health Sciences and Molecular Biotechnology Center, University of Torino, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Mercurio
authors.affiliation: Department of Molecular Biotechnology and Health Sciences and Molecular Biotechnology Center, University of Torino, Italy emanuela.tolosano@unito.it.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Tolosano
mesh_terms: D000818:Animals; D053898:Biosynthetic Pathways; D002454:Cell Differentiation; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis / Q000502:physiology*; D005786:Gene Expression Regulation; D006402:Hematologic Diseases / Q000235:genetics / Q000378:metabolism; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism
chemical_list: D006418:Heme