Role of Bcl-2 family members in anoxia induced cell death.
Anoxia, the condition of oxygen deprivation, induces apoptosis via the intrinsic apoptotic pathway. Cells deficient in both Bax and Bak do not undergo cell death during anoxia. However, the underlying mechanism of anoxia induced cell death is not well defined. Here we report our latest findings of two critical events that are required to induce cell death during anoxia. First, a key member of the Bcl-2 family of pro-survival proteins, Mcl-1, undergoes proteasomal-dependent degradation. The loss of Mcl-1 protein is independent of Bax or Bak indicating this is an early event in the apoptotic cascade. Second, cells inhibit the mitochondrial electron transport chain to negate the pro-survival function of Bcl-2/Bcl-X(L). These observations indicate that loss of pro-survival function is necessary for anoxia induced cell death.
Shroff
Emelyn H
EH
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Snyder
Colleen
C
Chandel
Navdeep S
NS
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D004579:Electron Transport / Q000502:physiology; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D046988:Proteasome Endopeptidase Complex