FIGURE 3.

Connection between cofactor assembly pathways of the RNR and the mitochondrial (ISC) and cytosolic (CIA) iron-sulfur protein biosynthetic pathways in S. cerevisiae. Apo-β₂ and -β′₂ rapidly form apo-ββ′. Assembly of Fe^III₂-Y^• in ββ′ is facilitated by β′, which stabilizes β in a conformation that allows iron binding. The [2Fe-2S]-bridged homodimer of Grx3 (Grx4) or heterodimer of Grx3/Grx4 is proposed to be required directly or indirectly for iron delivery to proteins involved in Fe-S cluster biosynthesis. The [2Fe-2S]²⁺ cluster of Dre2 receives an electron from NADPH via the FAD/FMN in Tah18 and is proposed to deliver it to β in RNR and to early step(s) in CIA (between Cfd1 and Nbp35). Assembly of the [2Fe-2S] clusters in Grx3/4 and Dre2 requires the mitochondria ISC, but not the cytosolic ISC machinery. Genetic and physical interactions have been observed between Dre2 and Grx3, although a mechanistic understanding of these interactions is lacking.