{"id":{"repo_id":"temple","oai_identifier":"oai:scholarshare.temple.edu:20.500.12613/6821"},"canonical_url":"https://search.dev.ndltd.org/etd/temple/oai:scholarshare.temple.edu:20.500.12613/6821","repository":{"repo_id":"temple","name":"Temple University","base_url":"https://scholarshare.temple.edu/server/oai/request"},"display":{"title":"N-ethylmaleimide sensitive factor (NSF) is a regulator of plasma membrane rupture and necrotic cell death","abstract":"Necrosis, originally considered chaotic, has been found to be regulated by distinct molecular pathways. To identify novel regulators of plasma membrane rupture, a hallmark of necrotic cell death, a genome-wide shRNA loss-of-function screen was performed. We identified SNARE complex members, mediators of canonical membrane fusion events, as necessary for Ca2+ and ROS-induced plasma membrane rupture andnecrosis. We targeted N-ethylmaleimide sensitive factor (NSF) due to its requirement in SNARE recycling, lack of gene homologs, and redox sensitivity. Deletion of Nsf protected against membrane rupture induced by various necrotic stimuli, yet did not influence apoptosis, suggesting specificity in programmed necrosis. We discovered that NSF localizes to sites of membrane blebbing and rupture. Additionally, SNARE-binding, ATPase activity, and redox modification are necessary for NSF’s role in necrosis. We generated conditional Nsf knockout mice and induced skeletal muscle injury via cardiotoxin injection. Loss of NSF protected against sarcolemmal rupture and myocyte death. Complementarily, cardiomyocyte-specific deletion of Nsf protected against ischemia-reperfusion injury. The SNARE complex regulator, NSF, is a key mediator of membrane rupture in necrotic cell death and a promising therapeutic target for numerous diseases.","abstract_html":"Necrosis, originally considered chaotic, has been found to be regulated by distinct molecular pathways. To identify novel regulators of plasma membrane rupture, a hallmark of necrotic cell death, a genome-wide shRNA loss-of-function screen was performed. We identified SNARE complex members, mediators of canonical membrane fusion events, as necessary for Ca2+ and ROS-induced plasma membrane rupture andnecrosis. We targeted N-ethylmaleimide sensitive factor (NSF) due to its requirement in SNARE recycling, lack of gene homologs, and redox sensitivity. Deletion of Nsf protected against membrane rupture induced by various necrotic stimuli, yet did not influence apoptosis, suggesting specificity in programmed necrosis. We discovered that NSF localizes to sites of membrane blebbing and rupture. Additionally, SNARE-binding, ATPase activity, and redox modification are necessary for NSF’s role in necrosis. We generated conditional Nsf knockout mice and induced skeletal muscle injury via cardiotoxin injection. Loss of NSF protected against sarcolemmal rupture and myocyte death. Complementarily, cardiomyocyte-specific deletion of Nsf protected against ischemia-reperfusion injury. The SNARE complex regulator, NSF, is a key mediator of membrane rupture in necrotic cell death and a promising therapeutic target for numerous diseases.","abstract_has_math":false,"creators":["Murray, Emma"],"institution":"Temple University. Libraries","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Elrod, John W."],"committee_chairs":[],"committee_members":["Kishore, Raj","Tian, Ying","Soboloff, Jonathan","Calvert, John W."],"year":2021,"date_issued":"2021","date_published":"2021","updated_at":"2026-07-27T21:21:38Z","subjects":["Cellular biology"],"languages":["eng"],"rights":["IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available."],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/20.500.12613/6821","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Elrod, John W."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Kishore, Raj","Tian, Ying","Soboloff, Jonathan","Calvert, John W."]},{"key":"dc:creator","label":"Author","values":["Murray, Emma"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2021-08-23T17:44:23Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2021-08-23T17:44:23Z"]},{"key":"dc:date.issued","label":"Date","values":["2021"]},{"key":"dc:publisher","label":"Institution","values":["Temple University. 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Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available."]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/20.500.12613/6821"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Necrosis, originally considered chaotic, has been found to be regulated by distinct molecular pathways. To identify novel regulators of plasma membrane rupture, a hallmark of necrotic cell death, a genome-wide shRNA loss-of-function screen was performed. We identified SNARE complex members, mediators of canonical membrane fusion events, as necessary for Ca2+ and ROS-induced plasma membrane rupture andnecrosis. We targeted N-ethylmaleimide sensitive factor (NSF) due to its requirement in SNARE recycling, lack of gene homologs, and redox sensitivity. Deletion of Nsf protected against membrane rupture induced by various necrotic stimuli, yet did not influence apoptosis, suggesting specificity in programmed necrosis. We discovered that NSF localizes to sites of membrane blebbing and rupture. Additionally, SNARE-binding, ATPase activity, and redox modification are necessary for NSF’s role in necrosis. We generated conditional Nsf knockout mice and induced skeletal muscle injury via cardiotoxin injection. Loss of NSF protected against sarcolemmal rupture and myocyte death. Complementarily, cardiomyocyte-specific deletion of Nsf protected against ischemia-reperfusion injury. The SNARE complex regulator, NSF, is a key mediator of membrane rupture in necrotic cell death and a promising therapeutic target for numerous diseases."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph.D."]},{"key":"dc:title","label":"Title","values":["N-ethylmaleimide sensitive factor (NSF) is a regulator of plasma membrane rupture and necrotic cell death"]}]}],"canonical_facts":{"dc:contributor.advisor":["Elrod, John W."],"dc:contributor.committeemember":["Kishore, Raj","Tian, Ying","Soboloff, Jonathan","Calvert, John W."],"dc:creator":["Murray, Emma"],"dc:date.accessioned":["2021-08-23T17:44:23Z"],"dc:date.available":["2021-08-23T17:44:23Z"],"dc:date.issued":["2021"],"dc:description.abstract":["Necrosis, originally considered chaotic, has been found to be regulated by distinct molecular pathways. To identify novel regulators of plasma membrane rupture, a hallmark of necrotic cell death, a genome-wide shRNA loss-of-function screen was performed. We identified SNARE complex members, mediators of canonical membrane fusion events, as necessary for Ca2+ and ROS-induced plasma membrane rupture andnecrosis. We targeted N-ethylmaleimide sensitive factor (NSF) due to its requirement in SNARE recycling, lack of gene homologs, and redox sensitivity. Deletion of Nsf protected against membrane rupture induced by various necrotic stimuli, yet did not influence apoptosis, suggesting specificity in programmed necrosis. We discovered that NSF localizes to sites of membrane blebbing and rupture. Additionally, SNARE-binding, ATPase activity, and redox modification are necessary for NSF’s role in necrosis. We generated conditional Nsf knockout mice and induced skeletal muscle injury via cardiotoxin injection. Loss of NSF protected against sarcolemmal rupture and myocyte death. Complementarily, cardiomyocyte-specific deletion of Nsf protected against ischemia-reperfusion injury. The SNARE complex regulator, NSF, is a key mediator of membrane rupture in necrotic cell death and a promising therapeutic target for numerous diseases."],"dc:description.degree":["Ph.D."],"dc:identifier.uri":["http://hdl.handle.net/20.500.12613/6821"],"dc:language.iso":["eng"],"dc:publisher":["Temple University. Libraries"],"dc:rights":["IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available."],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:subject":["Cellular biology"],"dc:title":["N-ethylmaleimide sensitive factor (NSF) is a regulator of plasma membrane rupture and necrotic cell death"],"dc:type":["Text"]},"updated_at":"2026-07-27T21:21:38Z"}