{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zangari J"],"funding":["Oncosuisse","Swiss National Science Foundation","Deutsche Forschungsgemeinschaft","Deutsche Forschungsgemeinschaft (German Research Foundation)","Fondation Ernst et Lucie Schmidheiny","Oncosuisse (OCS)"],"pagination":["1646-1662"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12373508"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(8)"],"pubmed_abstract":["Selective targeting of cancer cells is a major challenge for cancer therapy. Many cancer cells overexpress the cystine/glutamate antiporter xCT/CD98, an L-cystine transport system that strengthens antioxidant defences, thereby promoting tumour survival and progression. Here, we show that the D-enantiomer of cysteine (D-Cys) is selectively imported into xCT/CD98-overexpressing cancer cell lines and impairs their proliferation, particularly under high oxygen concentrations. Intracellular D-Cys specifically inhibits the mitochondrial cysteine desulfurase NFS1, a key enzyme of cellular iron-sulfur protein biogenesis, by blocking sulfur mobilization due to steric constraints. NFS1 inhibition by D-Cys affects all cellular iron-sulfur cluster-dependent functions, including mitochondrial respirati"],"journal":["Nature metabolism"],"pubmed_title":["D-cysteine impairs tumour growth by inhibiting cysteine desulfurase NFS1."],"pmcid":["PMC12373508"],"funding_grant_id":["KFS-4434-02-2018","Koselleck grant LI 415/6 and SPP 1927; LI 415/7","179421"],"pubmed_authors":["Zuhra K","Tsukamoto T","Cerezo M","Lill R","Schulz V","Freibert SA","Boniecki MT","Maundrell K","Vartholomaiou E","Martinou JC","Hanschke S","Ferre SM","Cygler M","Szabo C","Rouaud F","Gonzalez-Ruiz V","Rudaz S","Serre-Beinier V","Montessuit S","Stehling O","Zangari J","Bhattacharya K"],"additional_accession":[]},"is_claimable":false,"name":"D-cysteine impairs tumour growth by inhibiting cysteine desulfurase NFS1.","description":"Selective targeting of cancer cells is a major challenge for cancer therapy. Many cancer cells overexpress the cystine/glutamate antiporter xCT/CD98, an L-cystine transport system that strengthens antioxidant defences, thereby promoting tumour survival and progression. Here, we show that the D-enantiomer of cysteine (D-Cys) is selectively imported into xCT/CD98-overexpressing cancer cell lines and impairs their proliferation, particularly under high oxygen concentrations. Intracellular D-Cys specifically inhibits the mitochondrial cysteine desulfurase NFS1, a key enzyme of cellular iron-sulfur protein biogenesis, by blocking sulfur mobilization due to steric constraints. NFS1 inhibition by D-Cys affects all cellular iron-sulfur cluster-dependent functions, including mitochondrial respirati","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-08T06:48:47.386Z","creation":"2026-04-07T23:31:07.794Z"},"accession":"S-EPMC12373508","cross_references":{"pubmed":["40797101"],"doi":["10.1038/s42255-025-01339-1"]}}