{"doi":"10.1101/2021.08.18.456897","title":"Chlamydomonas ATX1 is essential for Cu distribution towards the secretory pathway and maintenance of biomass in conditions demanding cupro-enzyme dependent metabolic pathways","abstract":"Abstract Copper (Cu) chaperones, of which yeast ATX1 is a prototype, are small proteins with a Cu(I) binding Mx-CxxC motif, and are responsible for directing intracellular Cu towards specific client protein targets that use Cu as a cofactor. The Chlamydomonas reinhardtii ATX1 (CrATX1) was identified because of its high sequence similarity with yeast ATX1. Like the yeast homologue, CrATX1 accumulates in iron-deficient cells (but is not impacted by other metal-deficiencies), and YFP-ATX1 is distributed in the cytoplasm. Reverse genetic analysis using artificial microRNA (amiRNA) to generate lines with reduced CrATX1 abundance and CRISPR/CPF1 to generate ATX1 knock out lines validated a function for ATX1 in iron-poor cells, most likely because of an impact on metalation of the multicopper oxidase FOX1, which is an important component in high-affinity iron uptake. A more general impact on the secretory pathway is indicated by reduced growth of ATX1 mutant lines on guanine as a sole nitrogen source, which we attribute to loss of function of UOX1, a urate oxidase involved in guanine assimilation. The block of Cu trafficking towards the secretory pathway in ATX1 mutants is strikingly evident by a reduced amount of intracellular Cu in all conditions probed in this work.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":226191,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","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":271917,"name":"Sabeeha Merchant","orcid":"0000-0002-2594-509X","position":2,"is_corresponding":false},{"id":280600,"name":"Daniela Strenkert","orcid":"0000-0002-3420-1332","position":3,"is_corresponding":false},{"id":829182,"name":"Keegan L. J. Pham","orcid":"0000-0001-6574-5474","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T23:54:34.185847Z","pmid":null,"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":[]}