Mitochondrial calcium function and dysfunction in the central nervous system

AbstractThe ability of isolated brain mitochondria to accumulate, store and release calcium has been extensively characterized. Extrapolation to the intact neuron led to predictions that the in situ mitochondria would reversibly accumulate Ca2+ when the concentration of the cation in the vicinity of the mitochondria rose above the ‘set-point’ at which uptake and efflux were in balance, storing Ca2+ as a complex with phosphate, and slowly releasing the cation when plasma membrane ion pumps lowered the cytoplasmic free Ca2+. Excessive accumulation of the cation was predicted to lead to activation of the permeability transition, with catastrophic consequences for the neuron. Each of these predictions has been confirmed with intact neurons, and there is convincing evidence for the permeability transition in cellular Ca2+ overload associated with glutamate excitotoxicity and stroke, while the neurodegenerative disease in which possible defects in mitochondrial Ca2+ handling have been most intensively investigated is Huntington's Disease. In this brief review evidence that mitochondrial Ca2+ transport is relevant to neuronal survival in these conditions will be discussed