A lipid signature of BAK-driven apoptotic pore formation.

Apoptotic cell death is regulated by the BCL-2 protein family, with clusters of BAK or BAX homodimers driving pore formation in the mitochondrial outer membrane via a poorly understood process. There is growing evidence that, in addition to BAK and BAX, lipids play an important role in pore formation. Towards a better understanding of the lipidic drivers of apoptotic pore formation in isolated mitochondria, two complementary approaches were taken.

Robust autoactivation for apoptosis by BAK but not BAX highlights BAK as an important therapeutic target.

BAK and BAX, which drive commitment to apoptosis, are activated principally by certain BH3-only proteins that bind them and trigger major rearrangements. One crucial conformation change is exposure of their BH3 domain which allows BAK or BAX to form homodimers, and potentially to autoactivate other BAK and BAX molecules to ensure robust pore formation and cell death. Here, we test whether full-length BAK or mitochondrial BAX that are specifically activated by antibodies can then activate other BAK or BAX molecules.

A subunit of the mediator complex regulates vertebrate neuronal development.

The unique profiles of gene expression dictate distinct cellular identity. How these profiles are established during development is not clear. Here we report that the mutant motionless (mot), identified in a genetic screen for mutations that affect neuronal development in zebrafish, displays deficits of monoaminergic neurons and cranial sensory ganglia, whereas expression of the pan-neuronal marker Hu is largely unperturbed; GABAergic and subsets of cranial motor neurons do not appear to be deficient.