{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Stolp ZD"],"funding":["NIAID NIH HHS","NHLBI NIH HHS","NINDS NIH HHS","NIGMS NIH HHS"],"pagination":["110647"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9074372"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["39(2)"],"pubmed_abstract":["Unicellular eukaryotes have been suggested as undergoing self-inflicted destruction. However, molecular details are sparse compared with the mechanisms of programmed/regulated cell death known for human cells and animal models. Here, we report a molecular cell death pathway in Saccharomyces cerevisiae leading to vacuole/lysosome membrane permeabilization. Following a transient cell death stimulus, yeast cells die slowly over several hours, consistent with an ongoing molecular dying process. A genome-wide screen for death-promoting factors identified all subunits of the AP-3 complex, a vesicle trafficking adapter known to transport and install newly synthesized proteins on the vacuole/lysosome membrane. To promote cell death, AP-3 requires its Arf1-GTPase-dependent vesicle trafficking function and the kinase Yck3, which is selectively transported to the vacuole membrane by AP-3. Video microscopy revealed a sequence of events where vacuole permeability precedes the loss of plasma membrane integrity. AP-3-dependent death appears to be conserved in the human pathogenic yeast Cryptococcus neoformans."],"journal":["Cell reports"],"pubmed_title":["Yeast cell death pathway requiring AP-3 vesicle trafficking leads to vacuole/lysosome membrane permeabilization."],"pmcid":["PMC9074372"],"funding_grant_id":["R01 AI152078","R21 AI144373","R01 HL059842","R01 AI153414","R01 GM077875","R21 NS127076","R01 AI052733","R21 AI115016"],"pubmed_authors":["Liu Y","Lin S","Pineda FJ","Hardwick JM","Kulkarni M","Jalisi A","Stolp ZD","Casadevall A","Teng X","Cunningham KW","Zhu C"],"additional_accession":[]},"is_claimable":false,"name":"Yeast cell death pathway requiring AP-3 vesicle trafficking leads to vacuole/lysosome membrane permeabilization.","description":"Unicellular eukaryotes have been suggested as undergoing self-inflicted destruction. However, molecular details are sparse compared with the mechanisms of programmed/regulated cell death known for human cells and animal models. Here, we report a molecular cell death pathway in Saccharomyces cerevisiae leading to vacuole/lysosome membrane permeabilization. Following a transient cell death stimulus, yeast cells die slowly over several hours, consistent with an ongoing molecular dying process. A genome-wide screen for death-promoting factors identified all subunits of the AP-3 complex, a vesicle trafficking adapter known to transport and install newly synthesized proteins on the vacuole/lysosome membrane. To promote cell death, AP-3 requires its Arf1-GTPase-dependent vesicle trafficking function and the kinase Yck3, which is selectively transported to the vacuole membrane by AP-3. Video microscopy revealed a sequence of events where vacuole permeability precedes the loss of plasma membrane integrity. AP-3-dependent death appears to be conserved in the human pathogenic yeast Cryptococcus neoformans.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2026-05-31T21:00:00.173Z","creation":"2025-02-19T04:21:08.062Z"},"accession":"S-EPMC9074372","cross_references":{"pubmed":["35417721"],"doi":["10.1016/j.celrep.2022.110647"]}}