| First Author | Llambi F | Year | 2011 |
| Journal | Mol Cell | Volume | 44 |
| Issue | 4 | Pages | 517-31 |
| PubMed ID | 22036586 | Mgi Jnum | J:180685 |
| Mgi Id | MGI:5306845 | Doi | 10.1016/j.molcel.2011.10.001 |
| Citation | Llambi F, et al. (2011) A unified model of mammalian BCL-2 protein family interactions at the mitochondria. Mol Cell 44(4):517-31 |
| abstractText | During apoptosis, the BCL-2 protein family controls mitochondrial outer membrane permeabilization (MOMP), but the dynamics of this regulation remain controversial. We employed chimeric proteins composed of exogenous BH3 domains inserted into a tBID backbone that can activate the proapoptotic effectors BAX and BAK to permeabilize membranes without being universally sequestered by all antiapoptotic BCL-2 proteins. We thus identified two "modes" whereby prosurvival BCL-2 proteins can block MOMP, by sequestering direct-activator BH3-only proteins ("MODE 1") or by binding active BAX and BAK ("MODE 2"). Notably, we found that MODE 1 sequestration is less efficient and more easily derepressed to promote MOMP than MODE 2. Further, MODE 2 sequestration prevents mitochondrial fusion. We provide a unified model of BCL-2 family function that helps to explain otherwise paradoxical observations relating to MOMP, apoptosis, and mitochondrial dynamics. |
