apoptosom

Apoptosom, a rarely used variant spelling of apoptosome, refers to the cytosolic multiprotein complex that activates initiator caspases during the intrinsic pathway of apoptosis. In mammals, the core components are apoptotic protease activating factor 1 (APAF1), cytochrome c released from mitochondria, and procaspase-9; together they assemble into a large wheel-like complex that serves as a platform for caspase activation.

Formation is triggered by mitochondrial outer membrane permeabilization, which releases cytochrome c into the cytosol. Cytochrome c binds APAF1 in the presence of dATP or ATP, prompting APAF1 to oligomerize into a heptameric apoptosome. The apoptosome then recruits procaspase-9 through CARD-CARD interactions, bringing procaspase-9 molecules into proximity. Dimerization and autocatalytic processing convert procaspase-9 into active caspase-9, which cleaves and activates executioner caspases such as caspase-3 and caspase-7, culminating in apoptosis.

Regulation is exerted at multiple levels. Inhibitor of apoptosis proteins (IAPs), notably XIAP, can bind and inhibit active caspases, while SMAC/DIABLO released from mitochondria antagonizes IAPs. Additional regulatory inputs include post-translational modifications and cellular stress signals.

Other organisms harbor related apoptosis-activating assemblies, such as Dark in Drosophila and CED-4/CED-3 in C. elegans, reflecting conserved principles of intrinsic cell death. Dysregulation of apoptosome activity is implicated in cancer and neurodegenerative diseases; therapeutic strategies sometimes aim to promote apoptosome formation or relieve IAP inhibition, whereas others seek to block it.

Note: The standard term in most literature is apoptosome; "apoptosom" is a rare or incorrect variant.