1.A.21.1.6
Bcl-XL of 289 aas, a C-tail-anchored mitochondrial outer membrane protein (Setoguchi et al. 2006). The BH4 domain of Bcl-XL, but not that of Bcl-2, selectively targets VDAC1 and inhibits apoptosis by decreasing VDAC1-mediated Ca²⁺ uptake into mitochondria (Monaco et al. 2015). The ER-mitochondrion interface is a critical cell-signaling junction whereby Bcl-xL dynamically interacts with type 3 inositol 1,4,5-trisphosphate receptors (IP3R3) to coordinate mitochondrial Ca²⁺ transfer and alters cellular metabolism in order to increase the cells' bioenergetic capacity, particularly during periods of stress (Williams et al. 2016).