Bcl-2 blocks apoptosis by preventing loss of mitochondrial outer membrane integrity

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Reduction of mitochondrial membrane potential (Ψm) and release of cytochrome c from mitochondria appear to be a key events during apoptosis. Apoptosis was induced in IC.DP premast cells by the withdrawal of IL-3. Ψm decreased by 12 h and cytochrome c was detected in the cytosol at 18 h. Despite these changes in the mitochondria after 18 h of IL-3 deprivation, clonogenicity was unaffected when IL-3 was replenished at 18 h. Activation of v-Abl tyrosine kinase in IC.DP cells before IL-3 depletion led to increased levels of Bcl-XL, prevented reduction of Ψm and the release of mitochondrial cytochrome c, and suppressed apoptosis. Activation of v-Abl TK 18 h after withdrawal of IL-3 when < 10% of the cells had died restored Ψm in the remaining cells. These data suggest that v-Abl TK or IL-3 can act downstream of the reduction in Ψm and cytochrome c release from mitochondria to promote long-term cell survival.