Caspase 9 is activated through the formation of an apoptosome, a multiprotein complex formed in response to cytochrome c release from the mitochondria. When cells are exposed to toxicants, mitochondrial outer membrane permeabilization occurs, leading to the release of cytochrome c into the cytosol. This event triggers the assembly of the apoptosome, which consists of cytochrome c, Apaf-1, and procaspase 9. The apoptosome facilitates the cleavage and activation of caspase 9, which then activates downstream effector caspases, such as caspase 3 and caspase 7, culminating in apoptosis.
