Mitochondria as biosensors of calcium microdomains

The notion that the agonist-dependent increases in intracellular Ca2+ conce ntration, on ubiquitous signalling mechanism, occur with a tightly regulate d spatio-temporal pattern has become an established concept in modern cell biology. As a consequence, the concept is emerging that the recruitment of specific intracellular targets and effector system mechanisms depends on ex posure to local [Ca2+] that differs substantially from the mean [Ca2+]. A s triking example is provided by mitochondria, intracellular organelles that have been overlooked for a long time in the field of calcium signalling due to the low affinity of their Ca2+- uptake pathways. We will summarize here some of the evidence indicating that these organelles actively participate in Ca2+ homeostasis in physiological conditions (with consequences not onl y for the control of their function, but also for the modulation of the com plexity of calcium signals) because they have the capability to respond to microdomains of high [Ca2+] transiently generated in their proximity by the opening of Ca2+ channels. (C) Harcourt Publishers Ltd.