{"doi":"10.1242/jcs.263571","title":"SLC-25A46 regulates mitochondrial fusion through the mitofusin protein FZO-1 and is essential for maintaining neuronal morphology","abstract":"Mitochondria are dynamic organelles shaped by sequential fission and fusion events. The mitochondrial protein SLC25A46 has been identified as a causative gene for mitochondrial neuropathies. However, the function of SLC25A46 in mitochondrial morphogenesis remains controversial, with several reports suggesting it acts as a mitochondrial fission factor, whereas others propose it as a fusion factor. In this study, employing forward genetics, we identified slc-25A46, a Caenorhabditis elegans ortholog of human SLC25A46, as an essential factor for mitochondrial fusion. Suppressor mutagenesis screening revealed loss-of-function mutations in drp-1, a mitochondrial fission factor, as suppressors of slc-25A46. The phenotype of slc-25A46 mutants is similar to that of mutants in the worm mitofusin ortholog fzo-1, wherein the mitochondrial fusion factor is disrupted. Overexpressing FZO-1 mitigated mitochondrial defects in slc-25a46 mutants, indicating that SLC-25A46 promotes fusion through FZO-1. Disease model worms carrying mutations associated with SLC25A46 exhibited mitochondrial fragmentation and accelerated neurodegeneration, suggesting that slc-25A46 maintains neuronal morphology through regulating mitochondrial fusion regulation.","journal":"Journal of Cell Science","year":2025,"id":525873,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9466,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1401410,"name":"Taisei Watanabe","orcid":null,"position":1,"is_corresponding":false},{"id":1400975,"name":"H. Takahashi","orcid":"0000-0002-6717-5441","position":2,"is_corresponding":false},{"id":1400976,"name":"Satoshi Shimo","orcid":"0000-0001-8256-6662","position":3,"is_corresponding":false},{"id":289048,"name":"Toshiyuki Oda","orcid":"0000-0001-8090-2159","position":4,"is_corresponding":false},{"id":655048,"name":"Asako Sugimoto","orcid":"0000-0001-6001-4293","position":5,"is_corresponding":false},{"id":252458,"name":"Shinsuke Niwa","orcid":"0000-0002-8367-9228","position":6,"is_corresponding":false},{"id":712128,"name":"Hiroyuki Obinata","orcid":null,"position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:50:25.860105Z","pmid":"40444356","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":[]}