Unpublished draft

APAF1

APAF1 (apoptotic protease-activating factor 1) is the cytosolic scaffold that assembles the apoptosome, the heptameric complex that activates caspase-9.

Function

When the mitochondrial outer membrane permeabilizes, cytochrome c escapes into the cytosol and binds APAF1. The binding, together with dATP, converts APAF1 from a folded-inactive monomer into an open form that oligomerizes into a seven-spoked wheel - the apoptosome. Each spoke presents a caspase recruitment domain that captures procaspase-9, dimerizes it, and thereby activates it; active caspase-9 then cleaves executioner caspases (caspase-3) and the cell dismantles itself. APAF1 activation is therefore the step at which mitochondrial outer-membrane permeabilization commits the cell to