{"doi":"10.1093/mtomcs/mfad043","title":"Zn deficiency disrupts Cu and S homeostasis in Chlamydomonas resulting in over accumulation of Cu and Cysteine","abstract":"Growth of Chlamydomonas reinhardtii in zinc (Zn) limited medium leads to disruption of copper (Cu) homeostasis, resulting in up to 40-fold Cu over-accumulation relative to its typical Cu quota. We show that Chlamydomonas controls its Cu quota by balancing Cu import and export, which is disrupted in a Zn deficient cell, thus establishing a mechanistic connection between Cu and Zn homeostasis. Transcriptomics, proteomics and elemental profiling revealed that Zn-limited Chlamydomonas cells up-regulate a subset of genes encoding \"first responder\" proteins involved in sulfur (S) assimilation and consequently accumulate more intracellular S, which is incorporated into L-cysteine, γ-glutamylcysteine, and homocysteine. Most prominently, in the absence of Zn, free L-cysteine is increased ∼80-fold, corresponding to ∼2.8 × 109 molecules/cell. Interestingly, classic S-containing metal binding ligands like glutathione and phytochelatins do not increase. X-ray fluorescence microscopy showed foci of S accumulation in Zn-limited cells that co-localize with Cu, phosphorus and calcium, consistent with Cu-thiol complexes in the acidocalcisome, the site of Cu(I) accumulation. Notably, cells that have been previously starved for Cu do not accumulate S or Cys, causally connecting cysteine synthesis with Cu accumulation. We suggest that cysteine is an in vivo Cu(I) ligand, perhaps ancestral, that buffers cytosolic Cu.","journal":"Metallomics","year":2023,"id":344650,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":271910,"name":"Stefan Schmollinger","orcid":"0000-0002-7487-8014","position":1,"is_corresponding":false},{"id":1083485,"name":"Yuntao Hu","orcid":"0000-0002-2409-9821","position":2,"is_corresponding":false},{"id":725466,"name":"Christian Hofmann","orcid":"0000-0003-0700-6520","position":3,"is_corresponding":false},{"id":1083486,"name":"K A Holbrook","orcid":"0000-0001-6923-3580","position":4,"is_corresponding":false},{"id":1084094,"name":"Helen W. Liu","orcid":null,"position":5,"is_corresponding":false},{"id":35316,"name":"Samuel Purvine","orcid":"0000-0002-2257-2400","position":6,"is_corresponding":false},{"id":255022,"name":"Carrie Nicora","orcid":"0000-0003-2461-9548","position":7,"is_corresponding":false},{"id":960257,"name":"Yanqi Luo","orcid":"0000-0001-5624-9583","position":8,"is_corresponding":false},{"id":563063,"name":"Mary Lipton","orcid":"0000-0001-7749-0077","position":9,"is_corresponding":false},{"id":240876,"name":"Trent R. Northen","orcid":"0000-0001-8404-3259","position":10,"is_corresponding":false},{"id":1083487,"name":"Stephan Clemens","orcid":"0000-0003-0570-1060","position":11,"is_corresponding":false},{"id":271917,"name":"Sabeeha Merchant","orcid":"0000-0002-2594-509X","position":12,"is_corresponding":false},{"id":280600,"name":"Daniela Strenkert","orcid":"0000-0002-3420-1332","position":0,"is_corresponding":true}],"reference_count":105,"raw_metadata":null,"created_at":"2026-07-19T01:11:35.133818Z","pmid":"37422438","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":[]}