The endoplasmic reticulum (ER) can elicit proapoptotic signalling that results 
in transmission of Ca(2+) to the mitochondria, which in turn stimulates 
recruitment of the fission enzyme DRP1 to the surface of the organelle. Here, we 
show that BH3-only BIK activates this pathway at the ER in intact cells, 
resulting in mitochondrial fragmentation but little release of cytochrome c to 
the cytosol. The BIK-induced transformations in mitochondria are dynamic in 
nature and involve DRP1-dependent remodelling and opening of cristae, where the 
major stores of cytochrome c reside. This novel function for DRP1 is distinct 
from its recognized role in regulating mitochondrial fission. Selective 
permeabilization of the outer membrane with digitonin confirmed that BIK 
stimulation results in mobilization of intramitochondrial cytochrome c. Of note, 
BIK can cooperate with a weak BH3-only protein that targets mitochondria, such 
as NOXA, to activate BAX by a mechanism that is independent of DRP1 enzyme 
activity. When expressed together, BIK and NOXA cause rapid release of mobilized 
cytochrome c and activation of caspases.