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Respiring mitochondria determine the pattern of activation and inactivation of the store‐operated Ca 2+ current I CRAC
Author(s) -
Gilabert Juan A.,
Parekh Anant B.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.23.6401
Subject(s) - endoplasmic reticulum , intracellular , cytosol , mitochondrion , biology , microbiology and biotechnology , biophysics , calcium signaling , membrane potential , biochemistry , enzyme
In eukaryotic cells, hormones and neurotransmitters that engage the phosphoinositide pathway evoke a biphasic increase in intracellular free Ca 2+ concentration: an initial transient release of Ca 2+ from intracellular stores is followed by a sustained phase of Ca 2+ influx. This influx is generally store dependent. Most attention has focused on the link between the endoplasmic reticulum and store‐operated Ca 2+ channels in the plasma membrane. Here, we describe that respiring mitochondria are also essential for the activation of macroscopic store‐operated Ca 2+ currents under physiological conditions of weak intracellular Ca 2+ buffering. We further show that Ca 2+ ‐dependent slow inactivation of Ca 2+ influx, a widespread but poorly understood phenomenon, is regulated by mitochondrial buffering of cytosolic Ca 2+ . Thus, by enabling macroscopic store‐operated Ca 2+ current to activate, and then by controlling its extent and duration, mitochondria play a crucial role in all stages of store‐operated Ca 2+ influx. Store‐operated Ca 2+ entry reflects a dynamic interplay between endoplasmic reticulum, mitochondria and plasma membrane.