Abstract
Iron is essential for many cellular processes, but cellular iron homeostasis must be maintained to ensure the balance of cellular signaling processes and prevent disease. Iron transport in and out of the cell and cellular organelles is crucial in this regard. The transport of iron into the mitochondria is particularly important, as heme and the majority of iron-sulfur clusters are synthesized in this organelle. Iron is also required for the production of mitochondrial complexes that contain these iron-sulfur clusters and heme. As the principal iron importers in the mitochondria of human cells, the mitoferrins have emerged as critical regulators of cytosolic and mitochondrial iron homeostasis. Here, we review the discovery and structure of the mitoferrins, as well as the significance of these proteins in maintaining cytosolic and mitochondrial iron homeostasis for the prevention of cancer and many other diseases.