Heme transport and erythropoiesis

Abstract

In humans, systemic heme homeostasis is achieved via coordinated regulation of heme synthesis, transport and degradation. Although the heme biosynthesis and degradation pathways have been well characterized, the pathways for heme trafficking and incorporation into hemoproteins remain poorly understood. In the past few years, researchers have exploited genetic, cellular and biochemical tools, to identify heme transporters and, in the process, reveal unexpected functions for this elusive group of proteins. However, given the complexity of heme trafficking pathways, current knowledge of heme transporters is fragmented and sometimes contradictory. This review seeks to focus on recent studies on heme transporters with specific emphasis on their functions during erythropoiesis.

Figure 1. A schematic description of known heme transporters

HRG-1 is a heme importer that localizes to endosomal/lysosomal compartments, but can traffic to the plasma membrane. HCP1 and FLVCR2 are two putative heme importers. The cell surface FLVCR1a and the ABC transporter ABCG2 have been implicated in heme export in erythroid cells, whereas the mitochondrial isoform FLVCR1b transport heme into the cytosol. ABCB6 was previously proposed to be a mitochondrial porphyrin/heme importer, but has recently been shown to localize to the plasma membrane and endosomal/lysosomal vesicles. ABCB10 forms a complex with MFRN1 and FECH, and stabilizes MFRN1. It is not clear whether ABCB10 transport heme. Heme carrier / chaperone that is responsible for intra- and intercellular heme trafficking remains unknown. Question marks represent the presumptive heme trafficking pathways. PM, plasma membrane.