Abstract:
:The proapoptotic Bcl-2 protein Bax is predominantly found in the cytosol of nonapoptotic cells and is commonly thought to translocate to mitochondria following an apoptotic stimulus. The current model for Bax activation is that BH3 proteins bind to cytosolic Bax, initiating mitochondrial targeting and outer-membrane permeabilization. Here, we challenge this and show that Bax is constitutively targeted to mitochondria but in nonapoptotic cells is constantly translocated back to the cytosol. Using live-cell spinning-disk confocal imaging with a combination of FLIP, FRAP, and photoactivatable GFP-Bax, we demonstrate that disrupting adhesion-dependent survival signals slows the rate of Bax's dissociation from mitochondria, leading to its accumulation on the outer mitochondrial membrane. The overall accumulation of mitochondrial Bax following loss of survival signaling sensitizes cells to proapoptotic BH3 proteins. Our findings show that Bax is normally in a dynamic equilibrium between cytosol and mitochondria, enabling fluctuations in survival signals to finely adjust apoptotic sensitivity.
journal_name
Mol Celljournal_title
Molecular cellauthors
Schellenberg B,Wang P,Keeble JA,Rodriguez-Enriquez R,Walker S,Owens TW,Foster F,Tanianis-Hughes J,Brennan K,Streuli CH,Gilmore APdoi
10.1016/j.molcel.2012.12.022subject
Has Abstractpub_date
2013-03-07 00:00:00pages
959-71issue
5eissn
1097-2765issn
1097-4164pii
S1097-2765(13)00034-8journal_volume
49pub_type
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