tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. This study shows that tBID, a truncated form of BID, functions as a membrane-targeted death ligand that binds to BAK on mitochondria, leading to the release of cytochrome c. The BH3 domain of tBID is essential for cytochrome c release but not for mitochondrial targeting. tBID induces the oligomerization of BAK, which forms a pore for cytochrome c efflux, integrating the pathway from death receptors to cell death. The study demonstrates that tBID activates BAK through an allosteric mechanism, leading to the release of cytochrome c and subsequent apoptosis. The findings suggest that tBID acts as a downstream effector in the mitochondrial apoptotic pathway, interacting with BAK to facilitate cytochrome c release. The results highlight the importance of tBID in the mitochondrial release of cytochrome c and the role of BAK in this process. The study also shows that tBID can function independently of the permeability transition pore, indicating that BAK oligomerization itself provides a pore for cytochrome c release. These findings contribute to the understanding of the molecular mechanisms underlying apoptosis and the role of tBID in the mitochondrial apoptotic pathway.tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. This study shows that tBID, a truncated form of BID, functions as a membrane-targeted death ligand that binds to BAK on mitochondria, leading to the release of cytochrome c. The BH3 domain of tBID is essential for cytochrome c release but not for mitochondrial targeting. tBID induces the oligomerization of BAK, which forms a pore for cytochrome c efflux, integrating the pathway from death receptors to cell death. The study demonstrates that tBID activates BAK through an allosteric mechanism, leading to the release of cytochrome c and subsequent apoptosis. The findings suggest that tBID acts as a downstream effector in the mitochondrial apoptotic pathway, interacting with BAK to facilitate cytochrome c release. The results highlight the importance of tBID in the mitochondrial release of cytochrome c and the role of BAK in this process. The study also shows that tBID can function independently of the permeability transition pore, indicating that BAK oligomerization itself provides a pore for cytochrome c release. These findings contribute to the understanding of the molecular mechanisms underlying apoptosis and the role of tBID in the mitochondrial apoptotic pathway.