Calcium signal transmission between endoplasmic reticulum (ER) and mitochondria is supported by a local [Ca2+] control that operates between IP3receptor Ca2+release channels (IP3R) and mitochondrial Ca2+uptake sites, and displays functional similarities to synaptic transmission. Activation of IP3R by IP3is known to evoke quantal Ca2+mobilization that is associated with incremental elevations of mitochondrial matrix [Ca2+] ([Ca2+]m). Here we report that activation of IP3R by adenophostin-A (AP) yields non-quantal Ca2+mobilization in mast cells. We also show that the AP-induced continuous Ca2+release causes relatively small [Ca2+]mresponses, in particular, the sustained phase of Ca2+release is not sensed by the mitochondria. Inhibition of ER Ca2+pumps by thapsigargin slightly increases IP3-induced [Ca2+]mresponses, but augments AP-induced [Ca2+]mresponses in a large extent. In adherent permeabilized cells exposed to elevated [Ca2+], ER Ca2+uptake fails to affect global cytosolic [Ca2+], but attenuates [Ca2+]mresponses. 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 mechanism to attenuate the mitochondrial response during continuous Ca2+release through the IP3R or during gradual Ca2+influx to the junction between ER and mitochondria. © 2001 Harcourt Publishers Ltd.
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