Mechanism of sublethal mitochondrial permeabilization by BAX and BAK

BAX and BAK mediate Mitochondrial Outer Membrane Permeabilization (MOMP), a decisive step in apoptosis. Upon activation, they assemble into growing oligomers that open the apoptotic pore, releasing cytochrome c and SMAC to activate caspases and execute cell death. Additionally, the inner mitochondrial membrane becomes permeable, causing mitochondrial DNA to enter the cytosol and activating the cGAS/STING pathway and type I interferon responses, even at low caspase activity. Under sublethal conditions, minority MOMP can occur, with relevance to DNA instability, tumorigenesis, infections, and inflammatory signaling in senescent cells. The project aims to elucidate the molecular mechanisms of minority MOMP by BAX/BAK and regulate the transition to lethality.