Do Mammalian Cells Really Need to Export and Import Heme?

Heme is a cofactor that is essential to almost all forms of life. The production of heme is a balancing act between the generation of the requisite levels of the end-product and protection of the cell and/or organism against any toxic substrates, intermediates and, in this case, end-product. In this review, we provide an overview of our understanding of the formation and regulation of this metallocofactor and discuss new research on the cell biology of heme homeostasis, with a focus on putative transmembrane transporters now proposed to be important regulators of heme distribution. The main text is complemented by a discussion dedicated to the intricate chemistry and biochemistry of heme, which is often overlooked when new pathways of heme transport are conceived.