Microdomains with High Ca 2+ Close to IP 3 -Sensitive Channels that Are Sensed by Neighboring Mitochondria

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Abstract
Microdomains of high intracellular calcium ion concentration, [Ca 2+ ] i , have been hypothesized to occur in living cells exposed to stimuli that generate inositol 1,4,5-trisphosphate (IP 3 ). Mitochondrially targeted recombinant aequorin was used to show that IP 3 -induced Ca 2+ mobilization from intracellular stores caused increases of mitochondrial Ca 2+ concentration, [Ca 2+ ] m , the speed and amplitude of which are not accounted for by the relatively small increases in mean [Ca 2+ ] i . A similar response was obtained by the addition of IP 3 to permeabilized cells but not by perfusion of cells with Ca 2+ at concentrations similar to those measured in intact cells. It is concluded that in vivo, domains of high [Ca 2+ ] i are transiently generated close to IP 3 -gated channels and sensed by nearby mitochondria; this may provide an efficient mechanism for optimizing mitochondrial activity upon cell stimulation.