Oxygen deprivation induced cell death: an update.
Mammalian cells have multiple responses to low or zero oxygen concentrations. In the complete absence of oxygen, cells undergo cell death through apoptosis, and not necrosis. Apoptotic signaling during oxygen deprivation occurs through the release of cytochrome c and apaf-1 mediated caspase-9 activation. The upstream regulators of cytochrome c release are the Bcl-2 family members. Pro-apoptotic Bcl-2 family members such as bax or bak are clearly required to initiate cytochrome c/apaf-1/caspase-9 mediated cell death during oxygen deprivation. Here we review what is currently known oxygen deprivation induced cell death and speculate about initiating mechanisms resulting in the activation of pro-apoptotic Bcl-2 family members.
Brunelle
J K
JK
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA.
Chandel
N S
NS
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D003574:Cytochrome c Group / Q000378:metabolism; D004579:Electron Transport; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D015398:Signal Transduction; D014158:Transcription, Genetic; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein
C494772:BAK1 protein, human; C494826:BAX protein, human; D003574:Cytochrome c Group; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D019869:Phosphatidylinositol 3-Kinases; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases