In many apoptosis scenarios, the mitochondrial inner electrical transmembrane potential collapses, indicating the opening of large conductance channels through the inner membrane. In contrast, certain stimuli can induce rupture of the outer membrane of mitochondria and release of caspase-activation proteins. Most proteases are synthesized as precursors that have little if any catalytic activity. The precursor is usually converted to the active enzyme by proteolytic processing mediated either by another protease or by autocatalysis. Thus large amounts of precursor can be accumulated in advance and activated on demand.
Proteases can regulate their own activation, resulting in an exponential rate of activation.
Where there are proteases there are inhibitors, and these inhibitors regulate the concentration of active protease in the cell. Proteolytic reactions can be specific, determined by a combination of primary, secondary, or tertiary structures of protein substrates. Proteolysis that governs critical biological processes such as the cell cycle or cell death is highly specific and involves a restricted set of substrates. The various caspases share similarities in amino acid sequence, structure, and substrate specificity. Caspases are among the most specific of proteases with an unusual and absolute requirement for cleavage after aspartic acid and recognition of at least 4 amino acids terminal to the cleavage site.