{"doi":"10.1016/j.rbc.2024.100043","title":"Dysfunctional copper homeostasis in Caenorhabditis elegans affects genomic and neuronal stability","abstract":"While copper (Cu) is an essential trace element for biological systems due to its redox properties, excess levels may lead to adverse effects partly due to overproduction of reactive species. Thus, a tightly regulated Cu homeostasis is crucial for health. Cu dyshomeostasis and elevated labile Cu levels are associated with oxidative stress and neurodegenerative disorders, but the underlying mechanisms have yet to be fully characterized. Here, we used Caenorhabditis elegans loss-of-function mutants of the Cu chaperone ortholog atox-1 and the Cu binding protein ortholog ceruloplasmin to model Cu dyshomeostasis, as they display a shifted ratio of total Cu towards labile Cu. We applied highly selective and sensitive techniques to quantify metabolites associated to oxidative stress with focus on mitochondrial integrity, oxidative DNA damage and neurodegeneration all in the context of a disrupted Cu homeostasis. Our novel data reveal elevated oxidative stress, compromised mitochondria displaying reduced ATP levels and cardiolipin content. Cu dyshomeostasis further induced oxidative DNA damage and impaired DNA damage response as well as neurodegeneration characterized by behavior and neurotransmitter analysis. Our study underscores the essentiality of a tightly regulated Cu homeostasis as well as mitochondrial integrity for both genomic and neuronal stability. • Atox-1 and ceruloplasmin are crucial for proper Cu homeostasis. • Elevated oxidative stress due to Cu imbalance in C. elegans . • Disrupted Cu homeostasis compromised mitochondrial function. • Cu dyshomeostasis results in genomic and neuronal instability.","journal":"Redox Biochemistry and Chemistry","year":2024,"id":474264,"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":1,"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":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":739301,"name":"Anna Gremme","orcid":null,"position":1,"is_corresponding":false},{"id":1265293,"name":"Torben Meiners","orcid":null,"position":2,"is_corresponding":false},{"id":376643,"name":"Vera Schwantes","orcid":"0009-0004-8400-5315","position":3,"is_corresponding":false},{"id":1310850,"name":"Karsten Sarnow","orcid":null,"position":4,"is_corresponding":false},{"id":1044070,"name":"Alicia Thiel","orcid":"0009-0004-2548-9022","position":5,"is_corresponding":false},{"id":513065,"name":"Tanja Schwerdtle","orcid":"0000-0002-4873-7488","position":6,"is_corresponding":false},{"id":228267,"name":"Michael Aschner","orcid":"0000-0002-2619-1656","position":7,"is_corresponding":false},{"id":376645,"name":"Heiko Hayen","orcid":"0000-0002-4074-8545","position":8,"is_corresponding":false},{"id":376644,"name":"Julia Bornhorst","orcid":"0000-0002-4018-2406","position":9,"is_corresponding":false},{"id":738689,"name":"Ann-Kathrin Weishaupt","orcid":"0000-0002-1650-7899","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:06:09.108857Z","pmid":"39726988","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":[]}