{"doi":"10.1016/j.celrep.2024.113681","title":"Partial loss of MCU mitigates pathology in vivo across a diverse range of neurodegenerative disease models","abstract":"Mitochondrial calcium (Ca 2+ ) uptake augments metabolic processes and buffers cytosolic Ca 2+ levels; however, excessive mitochondrial Ca 2+ can cause cell death. Disrupted mitochondrial function and Ca 2+ homeostasis are linked to numerous neurodegenerative diseases (NDs), but the impact of mitochondrial Ca 2+ disruption is not well understood. Here, we show that Drosophila models of multiple NDs (Parkinson's, Huntington's, Alzheimer's, and frontotemporal dementia) reveal a consistent increase in neuronal mitochondrial Ca 2+ levels, as well as reduced mitochondrial Ca 2+ buffering capacity, associated with increased mitochondria-endoplasmic reticulum contact sites (MERCs). Importantly, loss of the mitochondrial Ca 2+ uptake channel MCU or overexpression of the efflux channel NCLX robustly suppresses key pathological phenotypes across these ND models. Thus, mitochondrial Ca 2+ imbalance is a common feature of diverse NDs in vivo and is an important contributor to the disease pathogenesis. The broad beneficial effects from partial loss of MCU across these models presents a common, druggable target for therapeutic intervention.","journal":"Cell Reports","year":2024,"id":422100,"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":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"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":1215733,"name":"Roberta Tufi","orcid":"0000-0001-7295-010X","position":1,"is_corresponding":false},{"id":1216409,"name":"Thomas P. Gleeson","orcid":null,"position":2,"is_corresponding":false},{"id":1216410,"name":"Kinga M. Kolodziej","orcid":null,"position":3,"is_corresponding":false},{"id":1215734,"name":"Susanna Campesan","orcid":"0000-0002-2580-0413","position":4,"is_corresponding":false},{"id":570154,"name":"Ana Terriente-Félix","orcid":"0000-0003-4948-6219","position":5,"is_corresponding":false},{"id":1215735,"name":"Lewis Collins","orcid":"0000-0002-3717-7526","position":6,"is_corresponding":false},{"id":817068,"name":"Federica De Lazzari","orcid":"0000-0003-4676-8851","position":7,"is_corresponding":false},{"id":890510,"name":"Flaviano Giorgini","orcid":"0000-0001-7881-9508","position":8,"is_corresponding":false},{"id":477547,"name":"Alexander J. Whitworth","orcid":"0000-0002-1154-6629","position":9,"is_corresponding":false},{"id":882086,"name":"Madeleine J. Twyning","orcid":"0000-0003-0656-9989","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T01:57:46.393290Z","pmid":"38236772","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":[]}