{"doi":"10.1111/mmi.15326","title":"Converging Roles of the Metal Transporter <scp>SMF11</scp> and the Ferric Reductase <scp>FRE1</scp> in Iron Homeostasis of <i>Candida albicans</i>","abstract":"Pathogenic fungi must appropriately sense the host availability of essential metals such as Fe. In Candida albicans and other yeasts, sensing of Fe involves mitochondrial Fe-S clusters. Yeast mutants for Fe-S cluster assembly sense Fe limitation even when Fe is abundant and hyperaccumulate Fe. We observe this same disrupted Fe sensing with C. albicans mutants of SMF11, a NRAMP transporter of divalent metals. Mutants of smf11 hyperaccumulate both Mn and Fe and the elevated Mn is secondary to Fe overload. As with Fe-S biogenesis mutants, smf11∆/∆ mutants show upregulation of ferric reductases that are normally repressed under high Fe, and Fe import is activated. However, unlike Fe-S biogenesis mutants, smf11∆/∆ mutants show no defects in mitochondrial Fe-S enzymes. Intriguingly, this exact condition of disrupted Fe sensing without inhibiting Fe-S clusters occurs with C. albicans fre1∆/∆ mutants encoding a ferric reductase. Mutants of fre1 and smf11 display similar perturbations in the cell wall, in filamentation and in the ROS burst of morphogenesis, a Fe-dependent process. As with FRE1, SMF11 is important for virulence in a mouse model for disseminated candidiasis. We propose a model in which FRE1 and SMF11 operate outside the mitochondrial Fe-S pathway to donate ferrous Fe for Fe sensing.","journal":"Molecular Microbiology","year":2024,"id":458766,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1285568,"name":"Marika S. David","orcid":null,"position":1,"is_corresponding":false},{"id":1285052,"name":"Shuyi Yang","orcid":"0000-0002-3181-175X","position":2,"is_corresponding":false},{"id":1285053,"name":"Ritu Garg","orcid":"0009-0007-0291-6839","position":3,"is_corresponding":false},{"id":2737,"name":"Luca Pinello","orcid":"0000-0003-1195-9607","position":4,"is_corresponding":false},{"id":328326,"name":"Brendan P. Cormack","orcid":"0000-0002-2554-9345","position":5,"is_corresponding":false},{"id":758505,"name":"Valeria Culotta","orcid":"0000-0002-3213-1326","position":6,"is_corresponding":false},{"id":1063511,"name":"Naisargi K. Patel","orcid":"0009-0003-5209-1928","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:03:50.608887Z","pmid":"39529282","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}