B709 Mitochondrial Control of Cell Death

. Mitochondrial membrane permeabilization (MMP) is a critical event of early apoptosis. MMP is regulated by proand anti-apoptotic members of the Bax/Bcl-2 family of proteins, via a process which may involve sessile mitochondrial proteins organized in the two membrane-spanning permeability transition pore complex (PTPC). Apoptotic MMP differentially affects the outer and the inner mitochondrial membranes (1-3). The inner mitochondrial membrane becomes permeable to solutes up to 1500 Da, yet retains matrix proteins in their normal localization. In contrast, the outer mitochondrial membrane becomes completely permeabilized to proteins, leading to the release of soluble proteins from the mitochondrial intermembrane space to an ectopic (extra mitochondrial) localization. Several intermembrane proteins can activate catabolic hydrolases involved in the apoptotic process (4). One such protein is cytochrome c, which participates in the caspase activation cascade. Another functionally important intermembrane protein is apoptosis inducing factor (AIF), which functions as a caspase-independent death effector (5).