title: Synthesis, delivery and regulation of eukaryotic heme and Fe-S cluster cofactors.
abstract: In humans, the bulk of iron in the body (over 75%) is directed towards heme- or Fe-S cluster cofactor synthesis, and the complex, highly regulated pathways in place to accomplish biosynthesis have evolved to safely assemble and load these cofactors into apoprotein partners. In eukaryotes, heme biosynthesis is both initiated and finalized within the mitochondria, while cellular Fe-S cluster assembly is controlled by correlated pathways both within the mitochondria and within the cytosol. Iron plays a vital role in a wide array of metabolic processes and defects in iron cofactor assembly leads to human diseases. This review describes progress towards our molecular-level understanding of cellular heme and Fe-S cluster biosynthesis, focusing on the regulation and mechanistic details that are essential for understanding human disorders related to the breakdown in these essential pathways.
authors.affiliation: Departments of Biochemistry and Molecular Biology, and Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Dulmini P
authors.initials: DP
authors.lastname: Barupala
authors.affiliation: Departments of Biochemistry and Molecular Biology, and Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Dzul
authors.affiliation: Department of Chemistry and Biochemistry, College of Charleston, Charleston, SC 29424, USA.
authors.forename: Pamela Jo
authors.initials: PJ
authors.lastname: Riggs-Gelasco
authors.affiliation: Departments of Biochemistry and Molecular Biology, and Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA. Electronic address: Timothy.Stemmler@wayne.edu.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Stemmler
mesh_terms: D000818:Animals; D005057:Eukaryotic Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006418:Heme / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008954:Models, Biological
chemical_list: D007506:Iron-Sulfur Proteins; D006418:Heme; D007501:Iron
keywords: Fe homeostasis; Fe-cofactor biosynthesis; Fe–S clusters; Heme; Iron