{"doi":"10.1091/mbc.e24-09-0412","title":"Resolving the two-body problem: A postulated role for the V0 sector of the V0V1-ATPase in exosome biogenesis and multivesicular body fate","abstract":"Because the discovery of the multivesicular body (MVB) as the origin of secreted vesicles or exosomes, the question arose and still looms-what distinguishes an MVB destined for fusion with the plasma membrane (EXO-MVB) facilitating exosome release from an MVB involved in transport of content to the lysosome (LYSO-MVB). Do they have independent origins? Hence, the two-body problem. We hypothesize that a key to this conundrum is the membrane spanning V0 sector of the proton pump, V0V1-ATPase. The V0V1-ATPase participates in the acidification of intracellular compartments, although V0 can function separately from V1 and different V0 isoforms are endowed with membrane binding capabilities that allow the V0V1-ATPase to selectively localize to different endocytic compartments including early and late endosomes and lysosomes. We propose that V0, in collaboration with cholesterol and phosphoinositides, plays a central role in the early endosome as a nucleation center to direct the de novo assembly of an EXO-MVB scaffold. The EXO-MVB scaffold may play multiple roles-operating as an assembly platform, participating in membrane fission as well as providing downstream navigational queues necessary for exosome secretion. Thus, V0 may represent an influential nexus, a starting point, in exosome biogenesis.","journal":"Molecular Biology of the Cell","year":2024,"id":507824,"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":0.9566,"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":617031,"name":"Philip D. Stahl","orcid":null,"position":1,"is_corresponding":false},{"id":318458,"name":"Crislyn D’Souza‐Schorey","orcid":"0000-0002-8389-055X","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T02:11:06.395600Z","pmid":"39705591","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":[]}