Sulfur transfer mechanisms

Sulfur transfer mechanisms refer to the complex biochemical pathways responsible for the mobilization and trafficking of sulfur atoms required for the synthesis of essential biological cofactors and the modification of macromolecules. These processes are primarily mediated by cysteine desulfurases, such as NFS1, and sulfurtransferases like Rhodanese (TST), which extract sulfur from L-cysteine or thiosulfate to form a persulfide intermediate (Lill, 2009; PMID: 19661910). This reactive sulfur is then relayed to various targets for the assembly of iron-sulfur (Fe-S) clusters, thiamine, molybdenum cofactor, and lipoic acid, which are critical for mitochondrial respiration and DNA repair (Mueller, 2006; PMID: 16730114). In clinical contexts, these mechanisms are highly relevant in oncology, as certain cancers—most notably lung adenocarcinoma—upregulate NFS1 to satisfy the increased demand for Fe-S clusters to combat oxidative stress and maintain metabolic homeostasis (Alvarez et al., 2017; PMID: 28847004). While 'sulfur transfer mechanisms' describes a biological process rather than a single molecular target, specific components of these pathways, particularly NFS1, are actively being investigated as therapeutic targets for drug development to selectively disrupt mitochondrial function in cancer cells.

Other names

Sulfur relay systemsSulfur metabolismSulfur traffickingPersulfide signaling pathwaysIron-sulfur cluster biogenesis

Inhibition of sulfur mobilization from cysteine or thiosulfate, preventing the formation of persulfide intermediates required for Fe-S cluster assembly and mitochondrial respiration.