Sorting of calcium signals at the junctions of endoplasmic reticulum and mitochondria

Calcium signal transmission between endoplasmic reticulum (ER) and mitochon dria is supported by a local [Ca2+] control that operates between IP3 recep tor Ca2+ release channels (IP3R) and mitochondrial Ca2+ uptake sites, and d isplays functional similarities to synaptic transmission. Activation of IP3 R by IP3 is known to evoke quantal Ca2+ mobilization that is associated wit h incremental elevations of mitochondrial matrix [Ca2+] ([Ca2+](m)). Here w e report that activation of IP3R by adenophostin-A (AP) yields non-quantal Ca2+ mobilization in mast cells. We also show that the AP-induced continuou s Ca2+ release causes relatively small [Ca2+](m) responses, in particular, the sustained phase of Ca2+ release is not sensed by the mitochondria. Inhi bition of ER Ca2+ pumps by thapsigargin slightly increases IP3-induced [Ca2 +](m) responses, but augments AP-induced [Ca2+](m) responses in a large ext ent. In adherent permeabilized cells exposed to elevated [Ca2+], ER Ca2+ up take fails to affect global cytosolic [Ca2+](,) but attenuates [Ca2+]m resp onses. Moreover, almost every mitochondrion exhibits a region very close to ER Ca2+ pumps visualized by BODIPY-FL-thapsigargin or SERCA antibody. Thus , at the ER-mitochondrial junctions, localized ER Ca2+ uptake provides a me chanism to attenuate the mitochondrial response during continuous Ca2+ rele ase through the IP3R or during gradual Ca2+ influx to the junction between ER and mitochondria. (C) 2001 Harcourt Publishers Ltd.