Microdomains with high Ca2+ close to IP3-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.
Rizzuto
R
R
Department of Biomedical Sciences, University of Padova, Italy.
Brini
M
M
Murgia
M
M
Pozzan
T
T
D000331:Aequorin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology; D006367:HeLa Cells; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D011993:Recombinant Fusion Proteins; D000331:Aequorin; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium