Bax and Bak (Bax/Bak) are essential pro-apoptotic proteins of the Bcl-2 family 
that trigger mitochondrial outer membrane permeabilization (MOMP) in a 
Bcl-2/Bcl-xL-inhibitable manner. We recently discovered a new stress-related 
function for Bax/Bak-regulation of nuclear protein redistribution (NPR) from the 
nucleus to cytoplasm. This effect was independent of Bax/Bak N-terminus exposure 
and not inhibited by Bcl-xL over-expression. Here, we studied the molecular 
mechanism governing this novel non-canonical response. Wild-type (WT) and mutant 
versions of Bax were re-expressed in Bax/Bak double-knockout mouse embryonic 
fibroblasts and their ability to promote NPR, apoptotic events, and changes in 
lamin A mobility was examined. Our results show that, in this system, Bax 
expression was sufficient to restore NPR such as in WT cells undergoing 
apoptosis. This activity of Bax was uncoupled from cytochrome c release from the 
mitochondria (indicative of MOMP) and required its membrane localization, α 
helices 5/6, and the Bcl-2 homology 3 (BH3) domain. Moreover, enrichment of Bax 
in the nuclear envelope by the so-called Klarsicht/ANC-1/Syne-1 homology domain 
effectively triggered NPR as in WT Bax, but without inducing MOMP or cell death. 
Bax-induced NPR was associated with impairment in lamin A mobility, implying a 
connection between these two nuclear envelope-associated events. Overall, the 
results indicate a new MOMP-independent, stress-induced Bax function on the 
nuclear envelope.