Mitochondrial iron–sulfur cluster assembly machinery (ISC machinery)

The mitochondrial iron–sulfur (Fe-S) cluster assembly (ISC) machinery is a highly conserved multi-protein system responsible for the synthesis of Fe-S clusters, which serve as essential cofactors for numerous proteins involved in respiration, DNA repair, and metabolism. In fungi, this machinery typically includes the cysteine desulfurase Nfs1, the scaffold protein Isu1, and various chaperones and electron donors that facilitate the transfer of clusters to target apoproteins. Because Fe-S clusters are vital for fungal viability and virulence, the components of this pathway are increasingly studied as potential antifungal targets. However, the high degree of structural and functional homology between fungal and human ISC components presents a significant challenge for achieving therapeutic selectivity. Effective drug development in this area focuses on identifying unique fungal motifs or exploiting differences in iron regulation to disrupt fungal growth without compromising host mitochondrial function.

Other names

Mitochondrial ISC systemIron-sulfur cluster biogenesis pathwayMitochondrial ISC assembly complexFungal iron-sulfur cluster machinery

Inhibition of iron acquisition or disruption of the enzymatic assembly of iron-sulfur clusters, leading to metabolic collapse and oxidative stress in fungal cells.