{"doi":"10.26508/lsa.201900527","title":"Defective nucleotide-dependent assembly and membrane fusion in Mfn2 CMT2A variants improved by Bax","abstract":"Mitofusins are members of the dynamin-related protein family of large GTPases that harness the energy from nucleotide hydrolysis to remodel membranes. Mitofusins possess four structural domains, including a GTPase domain, two extended helical bundles (HB1 and HB2), and a transmembrane region. We have characterized four Charcot-Marie-Tooth type 2A-associated variants with amino acid substitutions in Mfn2 that are proximal to the hinge that connects HB1 and HB2. A functional defect was not apparent in cells as the mitochondrial morphology of Mfn2-null cells was restored by expression of any of these variants. However, a significant fusion deficiency was observed in vitro, which was improved by the addition of crude cytosol extract or soluble Bax. All four variants had reduced nucleotide-dependent assembly in cis, but not trans, and this was also improved by the addition of Bax. Together, our data demonstrate an important role for this region in Mfn2 GTP-dependent oligomerization and membrane fusion and is consistent with a model where cytosolic factors such as Bax are masking molecular defects associated with Mfn2 disease variants in cells.","journal":"Life Science Alliance","year":2020,"id":77869,"datarank":0.8379431076695363,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.39627726079457015,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.39627726079457015,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":17,"citers_with_citation_signal":17,"citers_with_endowment":17,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"is_data_producer":true,"deposit_databanks":{"PDB":["2W6D","2J69","6JFK"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":406025,"name":"E.A. Engelhart","orcid":null,"position":1,"is_corresponding":false},{"id":405207,"name":"Suzanne Hoppins","orcid":"0000-0002-8070-3560","position":2,"is_corresponding":false},{"id":405206,"name":"Nyssa B. Samanas","orcid":"0000-0002-6593-1290","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-18T21:49:16.197289Z","pmid":"32245838","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":[]}