title: Resistance to caspase-independent cell death requires persistence of intact mitochondria.
abstract: During apoptosis, mitochondrial outer membrane permeabilization (MOMP) is often a point-of-no-return; death can proceed even if caspase activation is disrupted. However, under certain conditions, resistance to MOMP-dependent, caspase-independent cell death is observed. Mitochondrial recovery represents a key process in this survival. Live cell imaging revealed that during apoptosis not all mitochondria in a cell necessarily undergo MOMP. This incomplete MOMP (iMOMP) was observed in response to various stimuli and in different cell types regardless of caspase activity. Importantly, the presence of intact mitochondria correlated with cellular recovery following MOMP, provided that caspase activity was blocked. Such intact mitochondria underwent MOMP in response to treatment of cells with the Bcl-2 antagonist ABT-737, suggesting that the resistance of these mitochondria to MOMP lies at the point of Bax or Bak activation. Thus, iMOMP provides a critical source of intact mitochondria that permits cellular survival following MOMP.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Stephen W G
authors.initials: SW
authors.lastname: Tait
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Parsons
authors.forename: Fabien
authors.initials: F
authors.lastname: Llambi
authors.forename: Lisa
authors.initials: L
authors.lastname: Bouchier-Hayes
authors.forename: Samuel
authors.initials: S
authors.lastname: Connell
authors.forename: Cristina
authors.initials: C
authors.lastname: Muñoz-Pinedo
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000502:physiology; D020169:Caspases / Q000378:metabolism*; D018929:Cell Culture Techniques; D016923:Cell Death; D002463:Cell Membrane Permeability; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000502:physiology; D008928:Mitochondria / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C486752:SYNJ2BP protein, human; D049452:Green Fluorescent Proteins; D020169:Caspases