Biochemistry, Department of


Date of this Version



Dietz, J.V.; Fox, J.L.; Khalimonchuk, O. Down the Iron Path: Mitochondrial Iron Homeostasis and Beyond. Cells 2021, 10, 2198. cells10092198


© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license


Cellular iron homeostasis and mitochondrial iron homeostasis are interdependent. Mitochondria must import iron to form iron–sulfur clusters and heme, and to incorporate these cofactors along with iron ions into mitochondrial proteins that support essential functions, including cellular respiration. In turn, mitochondria supply the cell with heme and enable the biogenesis of cytosolic and nuclear proteins containing iron–sulfur clusters. Impairment in cellular or mitochondrial iron homeostasis is deleterious and can result in numerous human diseases. Due to its reactivity, iron is stored and trafficked through the body, intracellularly, and within mitochondria via carefully orchestrated processes. Here, we focus on describing the processes of and components involved in mitochondrial iron trafficking and storage, as well as mitochondrial iron–sulfur cluster biogenesis and heme biosynthesis. Recent findings and the most pressing topics for future research are highlighted.