Transport of heme synthesis intermediates and heme in metazoans

Transport of heme synthesis intermediates and heme in metazoans. A, heme is synthesized via a conserved eight-step pathway involving both mitochondrial and cytoplasmic enzymes. The intermediates ALA, CPgenIII, and PPIX and the substrate glycine need to be transported across mitochondrial membranes for the subsequent reactions. The solute carrier protein SLC25A38 may be involved in translocating glycine into mitochondria. The ATP-binding cassette transporter ABCB6 and the peripheral benzodiazepine receptor (PBR) were proposed to facilitate the import of CPgenIII into the mitochondria, whereas the 2-oxoglutarate carrier (OGC) and the adenine nucleotide translocator (ANT) may play a role in PPIX transport. The mechanisms for the export of ALA and the shuttling of heme precursors among the cytosolic enzymes are unknown. ALAS, aminolevulinic acid synthase; CPOX, coproporphyrinogen oxidase. B, the last step of heme biosynthesis occurs in the mitochondrial matrix. The nascent heme moiety must be translocated across membranes to multiple subcellular compartments where target hemoproteins reside. Heme can also be exported out of the cell or imported into the cell. The cell-surface FLVCR and the ABC transporter ABCG2 have been implicated in heme export in erythroid cells, whereas HRG-1 was identified as a heme importer. The question marks represent the presumptive heme trafficking pathways that are currently unclear. COX, cytochrome c oxidase; Cytb5, cytochrome b5.

Publication

Iron and Porphyrin Trafficking in Heme Biogenesis. (2010) Iman J. Schultz, et al. J Biol Chem. 2010 Aug 27;285(35):26753-26759. Figure: F2. All organisms Homo sapiens Drosophila melanogaster

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