Fig. 8. Scheme of stress-induced, Bax-dependent, NE-associated events and their potential interplay in mediating SIGRUNB/NPR and cell death.

Apoptotic stresses promote Bax-induced SIGRUNB/NPR. The mechanism whereby Bax promotes SIGUNB/NPR may involve a direct rupture of the NE or nesprin-1 and 2 redistribution, which may lead to their degradation. Alternatively, degradation of nesprin-1 but not nesprin-2 may lead to nesprin-1 redistribution. This results in loss of integrity of LINC complexes containing nesprin-1/2. The stress also promotes an interaction between Bax and nesprin-2, which require Bax-NT exposure and occurs mainly in close proximity to perinuclear mitochondria. The nesprin-2 that interacts with Bax may be within the NE or redistributed. All of these Bax-mediated effects may contribute to cell death either via SIGRUNB/NPR⁴², by abolishing the ability of LINC complexes to connect the nucleus to the certain cytoskeleton elements and by affecting Bax-induced MOMP. Dashed arrows represent the potential pathways.