JNK phosphorylation of Bim and Bmf, members of the BH3-only subgroup of Bcl2-related proteins, induces Bax-dependent apoptosis. The study shows that JNK phosphorylates Bim and Bmf, which are normally sequestered by motor complexes. Phosphorylation causes their release from these complexes, linking the JNK signaling pathway to the mitochondrial apoptotic machinery. Bim and Bmf are BH3-only proteins that promote apoptosis by binding to and displacing anti-apoptotic Bcl2 proteins, leading to Bax and Bak activation. JNK phosphorylates Bim and Bmf within the DLC binding motif, disrupting their interaction with motor complexes and releasing them to initiate apoptosis. This phosphorylation is crucial for the release of Bim and Bmf from sequestration, allowing them to activate the mitochondrial apoptotic pathway. The study also demonstrates that JNK phosphorylation of Bim on Thr-56 inhibits its binding to DLC1, leading to its release and increased apoptotic activity. These findings highlight the role of JNK in regulating apoptosis by phosphorylating BH3-only proteins, providing a molecular link between JNK signaling and the mitochondrial apoptotic pathway. The study also shows that JNK can induce apoptosis through two mechanisms: transcriptional induction of Bim expression and post-translational regulation of Bim function. The results suggest that JNK plays a critical role in apoptosis by phosphorylating BH3-only proteins, which then activate the Bax/Bak-dependent mitochondrial apoptotic pathway.JNK phosphorylation of Bim and Bmf, members of the BH3-only subgroup of Bcl2-related proteins, induces Bax-dependent apoptosis. The study shows that JNK phosphorylates Bim and Bmf, which are normally sequestered by motor complexes. Phosphorylation causes their release from these complexes, linking the JNK signaling pathway to the mitochondrial apoptotic machinery. Bim and Bmf are BH3-only proteins that promote apoptosis by binding to and displacing anti-apoptotic Bcl2 proteins, leading to Bax and Bak activation. JNK phosphorylates Bim and Bmf within the DLC binding motif, disrupting their interaction with motor complexes and releasing them to initiate apoptosis. This phosphorylation is crucial for the release of Bim and Bmf from sequestration, allowing them to activate the mitochondrial apoptotic pathway. The study also demonstrates that JNK phosphorylation of Bim on Thr-56 inhibits its binding to DLC1, leading to its release and increased apoptotic activity. These findings highlight the role of JNK in regulating apoptosis by phosphorylating BH3-only proteins, providing a molecular link between JNK signaling and the mitochondrial apoptotic pathway. The study also shows that JNK can induce apoptosis through two mechanisms: transcriptional induction of Bim expression and post-translational regulation of Bim function. The results suggest that JNK plays a critical role in apoptosis by phosphorylating BH3-only proteins, which then activate the Bax/Bak-dependent mitochondrial apoptotic pathway.