The article investigates the mechanism by which Bcl-2, a proto-oncogene product, inhibits apoptosis. The authors found that mitochondria contain a pre-formed protein, the apoptosis-inducing factor (AIF), which is released upon disruption of the mitochondrial inner membrane potential (ΔΨm). AIF causes chromatin condensation and DNA fragmentation in isolated nuclei in a cell-free system. Bcl-2, when preventing mitochondrial permeability transition (PT), also inhibits the release of AIF from isolated mitochondria. However, Bcl-2 does not affect the formation of AIF or its action on the nucleus. The study suggests that Bcl-2 prevents apoptosis by retaining an apoptogenic protease in mitochondria. The findings provide insights into the regulation of apoptosis by Bcl-2 and the role of AIF in the apoptotic process.The article investigates the mechanism by which Bcl-2, a proto-oncogene product, inhibits apoptosis. The authors found that mitochondria contain a pre-formed protein, the apoptosis-inducing factor (AIF), which is released upon disruption of the mitochondrial inner membrane potential (ΔΨm). AIF causes chromatin condensation and DNA fragmentation in isolated nuclei in a cell-free system. Bcl-2, when preventing mitochondrial permeability transition (PT), also inhibits the release of AIF from isolated mitochondria. However, Bcl-2 does not affect the formation of AIF or its action on the nucleus. The study suggests that Bcl-2 prevents apoptosis by retaining an apoptogenic protease in mitochondria. The findings provide insights into the regulation of apoptosis by Bcl-2 and the role of AIF in the apoptotic process.