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

Microdomains of high intracellular calcium ion concentration, Ca2+i, have been hypothesized to occur in living cells exposed to stimuli that generate inositol 1,4,5-trisphosphate (IP3). Mitochondrially targeted recombinant aequorin was used to show that IP3-induced Ca2+ mobilization from intracellular stores caused increases of mitochondrial Ca2+ concentration, Ca2+m, the speed and amplitude of which are not accounted for by the relatively small increases in mean Ca2+i. A similar response was obtained by the addition of IP3 to permeabilized cells but not by perfusion of cells with Ca2+ at concentrations similar to those measured in intact cells. It is concluded that in vivo, domains of high Ca2+i are transiently generated close to IP3-gated channels and sensed by nearby mitochondria; this may provide an efficient mechanism for optimizing mitochondrial activity upon cell stimulation.