Role of Bcl-2 Family Members in Anoxia Induced Cell Death

Anoxia, the condition of oxygen deprivation, induces apoptosis via the intrinsic apoptoticpathway. 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. Herewe report our latest findings of two critical events that are required to induce cell deathduring 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 independentof Bax or Bak indicating this is an early event in the apoptotic cascade. Second, cellsinhibit the mitochondrial electron transport chain to negate the pro-survival function of Bcl-2/Bcl-XL. These observations indicate that loss of pro-survival function is necessary foranoxia induced cell death.