Iron: Mitochondrial Iron Metabolism and the Synthesis of Iron–Sulfur Clusters

Abstract

Abstract Mitochondria play a major role in cellular iron metabolism. These organelles contain respiratory complexes that are rich in hemes and iron–sulfur clusters (ISCs), including [Fe 4 S 4 ], [Fe 3 S 4 ], and [Fe 2 S 2 ] clusters. Moreover, these organelles are able to synthesize ISCs on their own, even in isolation from the cell, in a process mediated by the ISC machinery housed therein. In order for iron to be used by the mitochondrial ISC machinery for new cluster synthesis, it must first transit from the environment into the cellular cytoplasm and from the cytoplasm into the mitochondria. In mitochondria, a regulated transit iron pool, recognized by a characteristic biophysical signature, is used for generating new Fe–S clusters. Iron levels in mitochondria are generally maintained by homeostatic controls, although in some settings iron accumulates in the form of ferric phosphate nanoparticles that remain invisible to the homeostatic control mechanism. This review summarizes recent genetic and biophysical results associated with mitochondrial iron metabolism and ISC assembly, primarily in yeast mitochondria.