Iron-Sulfur (Fe-S) cluster assembly involves the incorporation of iron and sulfur into Fe-S clusters. The assembly begins in the mitochondrial matrix and is mediated by the mitochondrial core ISC complex, which synthesizes a 2Fe-2S cluster from cysteine-derived sulfur and ferrous iron (Fe2+). 2Fe-2S can be assembled into 4Fe-4S clusters or exported into the cytosol where 4Fe-4S clusters can be made. 2Fe-2S and 4Fe-4S are then incorporated into mitochondrial, cytosolic and nuclear apoproteins. Fe-S clusters are mainly involved in electron transfer and storage but can also be directly involved in catalysis or mediate structural support. (Adapted from FBrf0238243.)