{"id":{"repo_id":"nus","oai_identifier":"oai:scholarbank.nus.edu.sg:10635/13181"},"canonical_url":"https://search.dev.ndltd.org/etd/nus/oai:scholarbank.nus.edu.sg:10635/13181","repository":{"repo_id":"nus","name":"National University of Singapore","base_url":"https://scholarbank.nus.edu.sg/oai/request"},"display":{"title":"Role and regulation of mitochondrial permeability transition in cell death","abstract":"The role of the Mitochondrial Permeability Transition (MPT) in apoptosis and necrosis is controversial. Here we show that the MPT regulates the release of cytochrome c for apoptosis during endoplasmic reticulum (ER) stress by remodeling the cristae junction (CJ). CEM cells were treated with the ER-stressor thapsigargin (THG) which led to cyclophilin-D-dependent mitochondrial release of the profusion GTPase Optic Atrophy 1 (OPA1), which controls CJ integrity, and cytochrome c leading to apoptosis. Interference RNA knockdown of Bax blocked OPA1 and cytochrome c release after THG treatment, but did not prevent the MPT showing that Bax was essential for cytochrome c release by MPT. In isolated mitochondria, MPT led to OPA1 and cytochrome c release independently of VDAC and the outer membrane indicating that the MPT is an inner membrane phenomenon. Lastly, the MPT was regulated by the electron transport chain since THG-induced cell death was inhibited in cells lacking mtDNA.","abstract_html":"The role of the Mitochondrial Permeability Transition (MPT) in apoptosis and necrosis is controversial. Here we show that the MPT regulates the release of cytochrome c for apoptosis during endoplasmic reticulum (ER) stress by remodeling the cristae junction (CJ). CEM cells were treated with the ER-stressor thapsigargin (THG) which led to cyclophilin-D-dependent mitochondrial release of the profusion GTPase Optic Atrophy 1 (OPA1), which controls CJ integrity, and cytochrome c leading to apoptosis. Interference RNA knockdown of Bax blocked OPA1 and cytochrome c release after THG treatment, but did not prevent the MPT showing that Bax was essential for cytochrome c release by MPT. In isolated mitochondria, MPT led to OPA1 and cytochrome c release independently of VDAC and the outer membrane indicating that the MPT is an inner membrane phenomenon. Lastly, the MPT was regulated by the electron transport chain since THG-induced cell death was inhibited in cells lacking mtDNA.","abstract_has_math":false,"creators":["ZHANG DAWEI"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2008,"date_issued":"2008-03-19","date_published":"2008-03-19","updated_at":"2026-07-24T03:31:38Z","subjects":["mitochondrial permeability transition, cytochrome c, OPA1, cyclophilin-D, cristae remodeling, apoptosis"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["ZHANG DAWEI"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2008-03-19"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://scholarbank.nus.edu.sg/handle/10635/13181"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["mitochondrial permeability transition, cytochrome c, OPA1, cyclophilin-D, cristae remodeling, apoptosis"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://scholarbank.nus.edu.sg/bitstreams/923fdded-059e-4831-9dc1-1ade7010568b/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The role of the Mitochondrial Permeability Transition (MPT) in apoptosis and necrosis is controversial. Here we show that the MPT regulates the release of cytochrome c for apoptosis during endoplasmic reticulum (ER) stress by remodeling the cristae junction (CJ). CEM cells were treated with the ER-stressor thapsigargin (THG) which led to cyclophilin-D-dependent mitochondrial release of the profusion GTPase Optic Atrophy 1 (OPA1), which controls CJ integrity, and cytochrome c leading to apoptosis. Interference RNA knockdown of Bax blocked OPA1 and cytochrome c release after THG treatment, but did not prevent the MPT showing that Bax was essential for cytochrome c release by MPT. In isolated mitochondria, MPT led to OPA1 and cytochrome c release independently of VDAC and the outer membrane indicating that the MPT is an inner membrane phenomenon. Lastly, the MPT was regulated by the electron transport chain since THG-induced cell death was inhibited in cells lacking mtDNA."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["3f187aa1784236f9d2b76b4916276737","339dab19a20e5f24e47712d62b43e6af"]},{"key":"dc:title","label":"Title","values":["Role and regulation of mitochondrial permeability transition in cell death"]}]}],"canonical_facts":{"dc:creator":["ZHANG DAWEI"],"dc:date.issued":["2008-03-19"],"dc:description.abstract":["The role of the Mitochondrial Permeability Transition (MPT) in apoptosis and necrosis is controversial. Here we show that the MPT regulates the release of cytochrome c for apoptosis during endoplasmic reticulum (ER) stress by remodeling the cristae junction (CJ). CEM cells were treated with the ER-stressor thapsigargin (THG) which led to cyclophilin-D-dependent mitochondrial release of the profusion GTPase Optic Atrophy 1 (OPA1), which controls CJ integrity, and cytochrome c leading to apoptosis. Interference RNA knockdown of Bax blocked OPA1 and cytochrome c release after THG treatment, but did not prevent the MPT showing that Bax was essential for cytochrome c release by MPT. In isolated mitochondria, MPT led to OPA1 and cytochrome c release independently of VDAC and the outer membrane indicating that the MPT is an inner membrane phenomenon. Lastly, the MPT was regulated by the electron transport chain since THG-induced cell death was inhibited in cells lacking mtDNA."],"dc:format.checksum.md5":["3f187aa1784236f9d2b76b4916276737","339dab19a20e5f24e47712d62b43e6af"],"dc:identifier.uri":["https://scholarbank.nus.edu.sg/bitstreams/923fdded-059e-4831-9dc1-1ade7010568b/download"],"dc:relation.isreferencedby":["https://scholarbank.nus.edu.sg/handle/10635/13181"],"dc:subject":["mitochondrial permeability transition, cytochrome c, OPA1, cyclophilin-D, cristae remodeling, apoptosis"],"dc:title":["Role and regulation of mitochondrial permeability transition in cell death"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T03:31:38Z"}