{"doi":"10.1242/jcs.235002","title":"Vac8 spatially confines autophagosome formation at the vacuole in <i>S. cerevisiae</i>","abstract":"<jats:title>ABSTRACT</jats:title>\n               <jats:p>Autophagy is initiated by the formation of a phagophore assembly site (PAS), the precursor of autophagosomes. In mammals, autophagosome formation sites form throughout the cytosol in specialized subdomains of the endoplasmic reticulum (ER). In yeast, the PAS is also generated close to the ER, but always in the vicinity of the vacuole. How the PAS is anchored to the vacuole and the functional significance of this localization are unknown. Here, we investigated the role of the PAS–vacuole connection for bulk autophagy in the yeast Saccharomyces cerevisiae. We show that Vac8 constitutes a vacuolar tether that stably anchors the PAS to the vacuole throughout autophagosome biogenesis via the PAS component Atg13. S. cerevisiae lacking Vac8 show inefficient autophagosome–vacuole fusion, and form fewer and smaller autophagosomes that often localize away from the vacuole. Thus, the stable PAS–vacuole connection established by Vac8 creates a confined space for autophagosome biogenesis between the ER and the vacuole, and allows spatial coordination of autophagosome formation and autophagosome–vacuole fusion. These findings reveal that the spatial regulation of autophagosome formation at the vacuole is required for efficient bulk autophagy.</jats:p>","journal":"Journal of Cell Science","year":2019,"id":621285,"datarank":0.6394019815561974,"base_score":4.2626798770413155,"endowment":4.2626798770413155,"self_citation_contribution":0.6394019815561974,"citation_network_contribution":0.0,"self_endowment_contribution":0.6394019815561974,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":70,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1604157,"name":"Rubén Gómez-Sánchez","orcid":null,"position":1,"is_corresponding":false},{"id":495905,"name":"Akif Ciftci","orcid":"0000-0002-8171-5846","position":2,"is_corresponding":false},{"id":1057325,"name":"Franziska Kriegenburg","orcid":"0000-0003-3478-6323","position":3,"is_corresponding":false},{"id":121771,"name":"Muriel Mari","orcid":null,"position":4,"is_corresponding":false},{"id":1604160,"name":"Raffaela Torggler","orcid":null,"position":5,"is_corresponding":false},{"id":474724,"name":"Mariya Licheva","orcid":"0000-0001-7722-7340","position":6,"is_corresponding":false},{"id":552345,"name":"Fulvio Reggiori","orcid":"0000-0003-2652-2686","position":7,"is_corresponding":false},{"id":474725,"name":"Claudine Kraft","orcid":"0000-0002-3324-4701","position":8,"is_corresponding":false},{"id":1604153,"name":"David M. Hollenstein","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Vac8 spatially confines autophagosome formation at the vacuole in <i>S. cerevisiae</i>","abstract":"<jats:title>ABSTRACT</jats:title>\n               <jats:p>Autophagy is initiated by the formation of a phagophore assembly site (PAS), the precursor of autophagosomes. In mammals, autophagosome formation sites form throughout the cytosol in specialized subdomains of the endoplasmic reticulum (ER). In yeast, the PAS is also generated close to the ER, but always in the vicinity of the vacuole. How the PAS is anchored to the vacuole and the functional significance of this localization are unknown. Here, we investigated the role of the PAS–vacuole connection for bulk autophagy in the yeast Saccharomyces cerevisiae. We show that Vac8 constitutes a vacuolar tether that stably anchors the PAS to the vacuole throughout autophagosome biogenesis via the PAS component Atg13. S. cerevisiae lacking Vac8 show inefficient autophagosome–vacuole fusion, and form fewer and smaller autophagosomes that often localize away from the vacuole. Thus, the stable PAS–vacuole connection established by Vac8 creates a confined space for autophagosome biogenesis between the ER and the vacuole, and allows spatial coordination of autophagosome formation and autophagosome–vacuole fusion. These findings reveal that the spatial regulation of autophagosome formation at the vacuole is required for efficient bulk autophagy.</jats:p>","is_dataset_classified":null,"base_score":4.2626798770413155,"endowment":4.2626798770413155,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31649143","pmcid":"PMC6899017","openalex_id":"https://openalex.org/W2981652808","authors":[],"funders":[{"funder_name":"Vienna Science and Technology Fund","grant_id":"VRG10-001","title":null},{"funder_name":"Austrian Science Fund","grant_id":"P25522-B20","title":null},{"funder_name":"Austrian Science Fund","grant_id":"P28113-B28","title":null},{"funder_name":"Austrian Science Fund","grant_id":"W1261","title":"Signaling Mechanisms in Cellular Homeostasis"},{"funder_name":"European Research Council","grant_id":"769065","title":"Cell-free reconstitution of autophagy to dissect molecular mechanisms"},{"funder_name":"European Research Council","grant_id":"765912","title":"Driving next generation autophagy researchers towards translation"},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"403222702","title":null},{"funder_name":"European Molecular Biology Organization","grant_id":"91217002","title":null},{"funder_name":"ZonMW","grant_id":"016.130.606","title":"A three-dimensional look into autophagy"},{"funder_name":"ALW Open Programme","grant_id":"ALWOP.310","title":null},{"funder_name":"ALW Open Programme","grant_id":"ALWOP.355","title":null},{"funder_name":"H2020 Marie Skłodowska-Curie Actions","grant_id":"713660","title":"Protecting patients with enhanced susceptibility to infections"},{"funder_name":"Austrian Science Fund FWF","grant_id":"P 28113","title":"Mechanisms and hierarchy in autophagosome formation"},{"funder_name":"Austrian Science Fund FWF","grant_id":"P 25522","title":"Architecture and function of the phagosome assembly site in autophagy"},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"unidentified","title":"unidentified"}],"total_grants":15,"fwci":5.2816,"citation_percentile":0.96477904,"influential_citations":0,"citation_trend":[{"year":2020,"count":12},{"year":2021,"count":12},{"year":2022,"count":12},{"year":2023,"count":12},{"year":2024,"count":15},{"year":2025,"count":5},{"year":2026,"count":2}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://jcs.biologists.org/content/joces/132/22/jcs235002.full.pdf","host_type":"journal"},{"url":"https://jcs.biologists.org/content/joces/132/22/jcs235002.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1242/jcs.235002","host_type":"publisher"},{"url":"https://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.235002/3509256/jcs235002.pdf","host_type":"publisher"},{"url":"http://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.235002/2061758/jcs_235002v1.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1242/jcs.235002","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31649143","host_type":"repository"},{"url":"https://research.rug.nl/en/publications/e3c8ee0f-7ced-43f4-93ec-c102a8e976ee","host_type":"repository"},{"url":"https://hdl.handle.net/11370/e3c8ee0f-7ced-43f4-93ec-c102a8e976ee","host_type":"repository"},{"url":"http://jcs.biologists.org/cgi/content/short/132/22/jcs235002","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6899017","host_type":"repository"},{"url":"https://pure.rug.nl/ws/files/109571519/jcs235002.full.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6899017","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1242/jcs.235002","host_type":""},{"url":"https://dx.doi.org/10.1242/jcs.235002","host_type":""},{"url":"https://doi.org/https://doi.org/10.1242/jcs.235002","host_type":""}],"fields_of_study":["Autophagy in Disease and Therapy","Endoplasmic Reticulum Stress and Disease","Cellular transport and secretion","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Autophagosomes","Autophagy","Membrane Proteins","Saccharomyces cerevisiae","Vacuoles","Saccharomyces cerevisiae Proteins","Vesicular Transport Proteins"],"keywords":["Vacuole","Autophagy","Autophagosome","Cell biology","Biology","Endoplasmic reticulum","Biogenesis","Cytosol","Cytoplasm","Biochemistry","Enzyme","Pas","Phagophore Assembly Site","Vac8","Saccharomyces cerevisiae Proteins","Vacuoles","Autophagosomes","Vesicular Transport Proteins","610","Membrane Proteins","Autophagie (Physiologie)","Saccharomyces cerevisiae","Research Article"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T13:56:38.639365Z","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":[]}