A popular model of BCL-2 and BAX involvement in apoptosis suggests that upon 
apoptosis induction cytosolic BAX translocates to the mitochondria, where it 
displays the pro-apoptotic function, which involves its homodimerization. BCL-2 
exerts anti-apoptotic function by forming heterodimers with BAX, thus 
neutralizing the pro-apoptotic activity of the latter. We have shown that 
irradiation of the human myeloma cell line RPMI-8226 induced apoptosis as 
determined by DNA degradation, cytochrome c release into cytoplasm and BCL-2 
caspase-mediated cleavage. BCL-2 protein was present only in the membrane 
fraction, whereas BAX was found both in cytosol and membranes isolated from 
non-irradiated cells. Radiation induced moderate redistribution of BAX from 
cytosol to membranes with a concomitant increase in BCL-2/BAX heterodimer 
formation. Rapid and transient BCL-2 phosphorylation in membrane fractions of 
irradiated cells did not affect BCL-2/BAX heterodimerization. We failed to 
detect any BAX/BAX homodimers in apoptotic cells. Our findings show that in 
irradiated RPMI-8226 cells the formation of BCL-2/BAX heterodimers correlates 
with apoptosis. We conclude that BCL-2/BAX heterodimers are negative regulators 
of death protection, and our data agree with those who propose that BCL-2 does 
not require BAX to exert its survival function.