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

Abstract

Calcium signal transmission between endoplasmic reticulum (ER) and mitochondria is supported by a local [Ca2+] control that operates between IP3 receptor Ca2+ release channels (IP3R) and mitochondrial Ca2+ uptake sites, and displays functional similarities to synaptic transmission. Activation of IP3R by IP3 is 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+]m responses, 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+]m responses, but augments AP-induced [Ca2+]m responses in a large extent. In adherent permeabilized cells exposed to elevated [Ca2+], ER Ca2+ uptake fails to affect global cytosolic [Ca2+], but attenuates [Ca2+]m responses. 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.