Schematic illustration of the molecules involved in the genesis of [Fe-S] clusters. Nfs1 supplies elemental sulphur for incorporation into a new [Fe-S] cluster with pyridoxal-5-phosphate (PLP) as a cofactor. Homodimeric IscU acts as a scaffold upon which the [Fe-S] cluster is built. Two atoms of Fe are delivered to the cluster machinery and the [Fe-S] cluster components are rearranged to form a single [2Fe-2S] cluster that is bridged between the 2 IscU subunits. Another [2Fe-2S] cluster may be formed on the cluster-containing scaffold complex, leading to the formation of a single [4Fe-4S] cluster (see “The mitochondrion is a major site of [Fe-S] synthesis” for further details).