Mitochondria in apoptosis: The suicide organelles

A profound alteration in mitochondrial function constitutes an obligatory early event of the apoptotic process of mammalian cells. The molecular mechanism accounting for this alteration is mitochondrial membrane permeabilization (MMP), which is regulated by proteins from the Bcl-2 family. Antiapoptotic Bcl-2-like proteins inhibit MMP, while proapoptotic proteins from the Bcl-2 family induce MMP. MMP is both sufficient and (mostly) necessary for apoptosis to occur. MMP results in mitochondrial failure as well as in the release of catabolic hydrolases and their activators from mitochondria and thus initiates the degradation phase of apoptosis. MMP and the activation of caspases constitute two intertwined phenomena, meaning that induction of MMP can trigger the activation of caspases while activated caspases induce MMP. The concept that MMP constitutes a central event of the apoptotic process has profound implications for the design of pharmacological strategies for apoptosis inhibition.