Cysteine desulfurase (NFS1) (NFS1)

Cysteine desulfurase (NFS1) is a critical pyridoxal-phosphate-dependent enzyme that catalyzes the conversion of L-cysteine to L-alanine and a sulfur-containing persulfide intermediate [11, 19]. This enzyme serves as the primary sulfur donor for the biogenesis of iron-sulfur (Fe-S) clusters, which are indispensable cofactors for dozens of proteins involved in cellular respiration, DNA repair, and iron homeostasis [6, 17]. In the context of oncology, NFS1 is recognized as a key therapeutic target because its overexpression in certain cancers, particularly lung adenocarcinoma and gastric cancer, protects cells from oxidative stress and ferroptosis by maintaining Fe-S cluster integrity in high-oxygen environments [4, 10, 20]. Therapeutic strategies currently under investigation include the use of selective small-molecule inhibitors like Compound 53 and inhibitory decoy substrates such as D-cysteine to sensitize tumors to ferroptotic cell death [1, 5, 13]. However, as NFS1 is a vital housekeeping enzyme, developing these therapies requires careful management of potential toxicities associated with the disruption of essential mitochondrial functions in healthy tissues [6, 20].

Other names

NFS1IscS homologNitrogen fixation 1Cysteine desulfurylaseNifS homolog

Selective inhibition of enzymatic activity or acting as a decoy substrate to disrupt sulfur mobilization, thereby impairing iron-sulfur cluster biogenesis and inducing ferroptosis [1, 2, 20].