Mitochondria and apoptosis: HQ or high-security prison?

Whether we view the mitochondria as the headquarters for the leader of a cr ack suicide squad or as a prison for the leader of a militant coup, the rol e of the mitochondria in the apoptotic process is now well established. Dur ing apoptosis the integrity of the mitochondria is breeched, the mitochondr ial transmembrane potential drops, the electron transport chain is disrupte d, and proteins from the mitochondrial intermembrane space (MIS) such as cy tochrome c are released into the cytosol, although not necessarily in that order. In the cytosol, cytochrome c forms part of a proteinaceous complex t hat directly activates caspase-9, one of the apical enzymes responsible for the dismantling of the cell. in this way a mitochondrial factor which is n ormally locked away from the rest of the cell can directly bigger apoptosis . The need to regulate the release of cytochrome c suggests that the mitoch ondria may be the decision center for whether a cell lives or dies. Various hypotheses have been formulated to explain how proteins of the MTS are rel eased and how this process is regulated. These include the Bcl-2-regulated opening of a permeability transition pore or an increase in mitochondrial t ransmembrane potential followed by outer membrane rupture. It remains to be clarified which mitochondria specific events are essential for apoptosis a nd which are merely consequences of apoptosis.