Heme is an iron-containing tetrapyrrole cofactor that is essential for metazoan life. Heme is synthesized in a highly conserved enzymatic pathway in the mitochondria and cytosol. We have identified a complex of interacting proteins which contains several members of the heme biosynthetic pathway, mitochondrial transport proteins, and proteins thought to mediate mitochondrial membrane morphology. We have termed this complex the mitochondrial heme metabolon. Progesterone receptor membrane component 1 (PGRMC1), a sparsely characterized heme-binding protein with diverse putative functions, was identified as part of this complex. My work has focused on dissecting the role of Pgrmc1 in heme synthesis. Our data suggest that Pgrmc1 regulates heme synthesis via interactions with the heme biosynthetic enzyme Ferrochelatase and other metabolon components. We have utilized in vitro and in vivo models, including human erythroid cell culture and zebrafish, to define the function of Pgrmc1 in heme synthesis and erythroid development. We have also begun work on PGRMC2, a paralogue of Pgrmc1, which may have an overlapping function. Our work supports a model in which the mitochondrial heme metabolon, including Pgrmc1, serves as an essential hub for the synthesis of heme, the regulation thereof, and for the intracellular distribution of heme post-synthesis.