biostudies-literaturePandey AAmerican Heart AssociationNIDDK NIH HHSNIA NIH HHSNational Institutes of HealthNIGMS NIH HHS539-49https://www.ebi.ac.uk/biostudies/studies/S-EPMC3462219biostudies-literatureUnknown12(5)Cysteine desulfurases generate a covalent persulfide intermediate from cysteine, and this activated form of sulfur is essential for the synthesis of iron-sulfur (Fe-S) clusters. In yeast mitochondria, there is a complete machinery for Fe-S cluster synthesis, including a cysteine desulfurase, Nfs1p. Here we show that following supplementation of isolated mitochondria with [(35)S]cysteine, a radiolabeled persulfide could be detected on Nfs1p. The persulfide persisted under conditions that did not permit Fe-S cluster formation, such as nucleotide and/or iron depletion of mitochondria. By contrast, under permissive conditions, the radiolabeled Nfs1p persulfide was greatly reduced and radiolabeled aconitase was formed, indicating transfer of persulfide to downstream Fe-S cluster recipients. NfsMitochondrionIdentification of a Nfs1p-bound persulfide intermediate in Fe-S cluster synthesis by intact mitochondria.PMC3462219R37 DK053953R37DK053953R01 GM087965GM08796509GRNT2260364AG030504R01 AG030504Pain DYoon HDancis APandey ALyver ERfalseIdentification of a Nfs1p-bound persulfide intermediate in Fe-S cluster synthesis by intact mitochondria.Cysteine desulfurases generate a covalent persulfide intermediate from cysteine, and this activated form of sulfur is essential for the synthesis of iron-sulfur (Fe-S) clusters. In yeast mitochondria, there is a complete machinery for Fe-S cluster synthesis, including a cysteine desulfurase, Nfs1p. Here we show that following supplementation of isolated mitochondria with [(35)S]cysteine, a radiolabeled persulfide could be detected on Nfs1p. The persulfide persisted under conditions that did not permit Fe-S cluster formation, such as nucleotide and/or iron depletion of mitochondria. By contrast, under permissive conditions, the radiolabeled Nfs1p persulfide was greatly reduced and radiolabeled aconitase was formed, indicating transfer of persulfide to downstream Fe-S cluster recipients. Nfs2012-01-01T00:00:00Z2012 Sep2025-04-04T00:48:34.445Z2019-03-27T00:58:35ZS-EPMC34622192281375410.1016/j.mito.2012.07.103