Energized mitochondria increase the dynamic range over which inositol 1,4,5-trisphosphate activates store-operated calcium influx

In eukaryotic cells, activation of cell surface receptors that couple to the phosphoinositide pathway evokes a biphasic increase in intracellular free Ca 2+ concentration: an initial transient phase reflecting Ca 2+ release from intracellular stores, followed by a plateau phase due to Ca 2+ influx....

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Bibliographic Details
Published in:The EMBO journal 2001-06, Vol.20 (11), p.2672-2679
Main Authors: Gilabert, Juan A., Bakowski, Daniel, Parekh, Anant B.
Format: Article
Language:English
Subjects:
5-trisphosphate
Animals
Calcium - metabolism
Calcium Channels - physiology
calcium influx
Egtazic Acid - pharmacology
Humans
inositol 1
Inositol 1,4,5-Trisphosphate - pharmacology
inositol 1,4,5‐trisphosphate
Jurkat Cells
Kinetics
Leukemia, Basophilic, Acute
mitochondria
Mitochondria - drug effects
Mitochondria - physiology
Models, Biological
Physiology
Rats
Tumor Cells, Cultured
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Summary:In eukaryotic cells, activation of cell surface receptors that couple to the phosphoinositide pathway evokes a biphasic increase in intracellular free Ca 2+ concentration: an initial transient phase reflecting Ca 2+ release from intracellular stores, followed by a plateau phase due to Ca 2+ influx. A major component of this Ca 2+ influx is store‐dependent and often can be measured directly as the Ca 2+ release‐activated Ca 2+ current (I CRAC ). Under physiological conditions of weak intracellular Ca 2+ buffering, respiring mitochondria play a central role in store‐operated Ca 2+ influx. They determine whether macroscopic I CRAC activates or not, to what extent and for how long. Here we describe an additional role for energized mitochondria: they reduce the amount of inositol 1,4,5‐trisphosphate (InsP 3 ) that is required to activate I CRAC . By increasing the sensitivity of store‐operated influx to InsP 3 , respiring mitochondria will determine whether modest levels of stimulation are capable of evoking Ca 2+ entry or not. Mitochondrial Ca 2+ buffering therefore increases the dynamic range of concentrations over which the InsP 3 is able to function as the physiological messenger that triggers the activation of store‐operated Ca 2+ influx.
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.1093/emboj/20.11.2672