The article discusses the mechanisms by which BCL-2 proteins induce mitochondrial outer membrane permeabilization (MOMP) during apoptosis. The BCL-2 family of proteins, which includes both pro- and anti-apoptotic members, plays a crucial role in regulating this process. The authors explore two main models: the "anti-apoptotic protein neutralization" model, where BH3-only proteins neutralize anti-apoptotic proteins to promote MOMP; and the "direct activation" model, where BH3-only proteins directly activate effector molecules like BAX and BAK to induce MOMP. They argue that both models are necessary to fully understand MOMP and apoptosis, and suggest that further research is needed to elucidate the complex interactions within the BCL-2 network. The article also highlights the potential implications of these findings for therapeutic strategies targeting BCL-2 proteins in cancer treatment.The article discusses the mechanisms by which BCL-2 proteins induce mitochondrial outer membrane permeabilization (MOMP) during apoptosis. The BCL-2 family of proteins, which includes both pro- and anti-apoptotic members, plays a crucial role in regulating this process. The authors explore two main models: the "anti-apoptotic protein neutralization" model, where BH3-only proteins neutralize anti-apoptotic proteins to promote MOMP; and the "direct activation" model, where BH3-only proteins directly activate effector molecules like BAX and BAK to induce MOMP. They argue that both models are necessary to fully understand MOMP and apoptosis, and suggest that further research is needed to elucidate the complex interactions within the BCL-2 network. The article also highlights the potential implications of these findings for therapeutic strategies targeting BCL-2 proteins in cancer treatment.