Fig. 3.

Heterogeneous calcium accumulation within and among individual mitochondria. Electron micrograph of a high pressure-frozen, freeze-substituted, cultured hippocampal neuron demonstrating that neighboring mitochondria respond differently to NMDA exposure (100 μM for 30 min). Although all mitochondria took up significant amounts of calcium, as indicated by the electron-dense calcium- and phosphorus-rich precipitates, some (arrowheads) have presumably undergone MPT, becoming swollen and releasing matrix material and apoptogenic proteins, while others (arrows) have not. Scale bar = 500 nm. Modified from [38]. The diagram below illustrates schematically how this heterogeneity can account for delayed cell death. Specifically, damaged mitochondria early on release factors necessary to activate downstream death signaling, but undamaged mitochondria that are not dysfunctional maintain energy production and other essential mitochondrial functions for the time period between injury and death.