{"doi":"10.32388/1ohszz","title":"VPS13D Mutations Affect Mitochondrial Homeostasis and Locomotion in Caenorhabditis elegans","abstract":"Mitochondria control cellular metabolism, serve as hubs for signaling and organelle communication, and are important for the health and survival of cells. _VPS13D_ encodes a cytoplasmic lipid transfer protein that regulates mitochondrial morphology, mitochondria and endoplasmic reticulum (ER) contact, quality control of mitochondria. _VPS13D_ mutations have been reported in patients displaying ataxic and spastic gait disorders with variable age of onset. Here we used CRISPR/Cas9 gene editing to create _VPS13D_ related-spinocerebellar ataxia-4 (SCAR4) missense mutations and C-terminal deletion in _VPS13D_’s orthologue _vps-13D_ in _C. elegans_. Consistent with SCAR4 patient movement disorders and mitochondrial dysfunction, _vps-13D_ mutant worms exhibit locomotion defects and abnormal mitochondrial morphology. Importantly, animals with a _vps-13D_ deletion or a N3017I missense mutation exhibited an increase in mitochondrial unfolded protein response (UPRmt). The cellular and behavioral changes caused by _VPS13D_ mutations in _C. elegans_ advance the development of animal models that are needed to study SCAR4 pathogenesis.","journal":"Qeios","year":2025,"id":562118,"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":0.9525,"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":1205180,"name":"Andrea Thackeray","orcid":null,"position":1,"is_corresponding":false},{"id":465350,"name":"Eric H. Baehrecke","orcid":"0000-0003-1683-5064","position":2,"is_corresponding":false},{"id":564496,"name":"Mark J. Alkema","orcid":"0000-0002-1311-5179","position":3,"is_corresponding":false},{"id":662202,"name":"Ruoxi Wang","orcid":"0000-0002-3828-899X","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:56:05.550545Z","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":[]}