Although altered Ca2+ homoeostasis is believed to be a primary cause of death for many cell types in response to toxic insults, the specific Ca2+-stimulated event responsible for directing cells down the death pathway has remained elusive. Recent publications support the hypothesis that mitochondrial Ca2+ sequestration is the critical event in induction of excitotoxic neuronal death. If similar pathways are involved in the induction of Ca2+-induced necrotic and apoptotic death, then agents that mimic the action of the anti-apoptotic protein Bcl-2 should be particularly useful. Our previous results provide evidence that Bcl-2 increases the maximal capacity of mitochondria to accumulate Ca2+ while providing resistance to Ca2+-induced respiratory damage. In addition, we have found that Bcl-2 can block Ca2+-ionophore-induced delayed cell death. These data predict that in response to a challenging mitochondrial Ca2+ load, Bcl-2-containing mitochondria would be capable of continuing bioenergetic function, potentially avoiding a catastrophic death signalling event.
Bcl-2 and Ca2+-mediated mitochondrial dysfunction in neural cell death
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Guy C. Brown, David G. Nicholls, Chris E. Cooper, Anne N. Murphy, Gary Fiskum; Bcl-2 and Ca2+-mediated mitochondrial dysfunction in neural cell death. Biochem Soc Symp 1 September 1999; 66 33–41. doi: https://doi.org/10.1042/bss0660033
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