The study investigates the role of tBID, a BH3-only protein, in the release of cytochrome c from mitochondria during apoptosis. tBID, upon activation by caspase cleavage following engagement of death receptors like TNFR1/Fas, oligomerizes BAK (a pro-apoptotic member of the BCL-2 family) to release cytochrome c. The BH3 domain of tBID is essential for this process, but not for mitochondrial targeting. tBID forms an allosteric interaction with BAK, leading to a conformational change in BAK that facilitates its oligomerization and subsequent cytochrome c release. This mechanism integrates the apoptotic pathway from death receptors to mitochondrial cytochrome c release, highlighting the role of BH3-only proteins in regulating apoptosis.The study investigates the role of tBID, a BH3-only protein, in the release of cytochrome c from mitochondria during apoptosis. tBID, upon activation by caspase cleavage following engagement of death receptors like TNFR1/Fas, oligomerizes BAK (a pro-apoptotic member of the BCL-2 family) to release cytochrome c. The BH3 domain of tBID is essential for this process, but not for mitochondrial targeting. tBID forms an allosteric interaction with BAK, leading to a conformational change in BAK that facilitates its oligomerization and subsequent cytochrome c release. This mechanism integrates the apoptotic pathway from death receptors to mitochondrial cytochrome c release, highlighting the role of BH3-only proteins in regulating apoptosis.