Control of apoptosis by IP3 and ryanodine receptor driven calcium signals

Intracellular calcium signals mediated by IP3 and ryanodine receptors (IP3R /RyR) play a central role in cell survival, but emerging evidence suggests that IP3R/RyR are also important in apoptotic cell death. Switch from the l ife program to the death program may involve coincident detection of proapo ptotic stimuli and calcium signals or changes in the spatiotemporal pattern of the calcium signal or changes at the lever of effecters activated by th e calcium signal (e.g. calpain, calcineurin). The fate of the cell is often determined in the mitochondria, where calcium spikes may support cell surv ival through stimulation of ATP production or initiate apoptosis via openin g of the permeability transition pore and release of apoptotic factors such as cytochrome c. The functional importance of these mitochondrial calcium signalling pathways has been underscored by the elucidation of a highly eff ective, local Ca2+ coupling between IP3R/RyR and mitochondrial Ca2+ uptake sites. This article will focus on the IP3R/RyR-dependent pathways to apopto sis, particularly on the mitochondrial phase of the death cascade. (C) 2000 Harcourt Publishers Ltd.