Resistance to caspase-independent cell death requires persistence of intact mitochondria.
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.
Tait
Stephen W G
SW
Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Parsons
Melissa J
MJ
Llambi
Fabien
F
Bouchier-Hayes
Lisa
L
Connell
Samuel
S
Muñoz-Pinedo
Cristina
C
Green
Douglas R
DR
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
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