Mitochondria - the suicide organelles

One of the near-to-invariant hallmarks of early apoptosis (programmed cell death) is mitochondrial membrane permeabilization (MMP). It appears that mi tochondria fulfill a dual role during the apoptotic process. On the one han d, they integrate multiple different pro-apoptotic signal transducing casca des into a common pathway initiated by MMP. On the other hand, they coordin ate the catabolic reactions accompanying late apoptosis by releasing solubl e proteins that are normally sequestered within the intermembrane space. In a recent study,((1)) Li et al. described a nuclear transcription factor (N ur77/TR1/ NGFI-B) that can translocate to mitochondrial membranes to induce MMP. Moreover, two groups((2,3)) identified a novel intermembrane protein (Smac/DIABLO) that specifically neutralizes the inhibitor of apoptosis (IAP ) proteins, thereby facilitating the activation of caspases, a class of pro teases activated during apoptosis, These findings refine our knowledge how MMP connects to the cellular suicide machinery. (C) 2001 John Wiley & Sons, Inc.