MITOCHONDRIAL CONTROL OF APOPTOSIS - THE ROLE OF CYTOCHROME-C

Mitochondrial cytochrome c (cyt c) has been found to have dual functio ns in controlling both cellular energetic metabolism and apoptosis. Th rough interaction with apoptotic protease activating factors (Apaf), c yt c can initiate the activation cascade of caspases once it is releas ed into the cytosol. The loss of a component of the mitochondrial elec tron transport chain also triggers the generation of superoxide. Altho ugh cyt c can be released independent of the mitochondrial permeabilit y transition (MPT), the accompanying cellular redox change can trigger the MPT. Since another apoptotic protease, AIF, is released by MPT, t he two separate pathways provide redundancy that ensures effective exe cution of the cell death program. Anti-apoptotic Bcl-2 family proteins function as gatekeepers to prevent the release of both cyt c and AIF. In spite of their stabilization effect on the mitochondrial outer mem brane, Bcl-2 proteins may also be involved in the direct binding of Ap af molecules as regulatory elements further downstream from the mitoch ondrial apoptotic signals. (C) 1998 Elsevier Science B.V. All rights r eserved.