Respiring mitochondria determine the pattern of activation and inactivation of the store-operated Ca2+ current ICRAC
Open Access
- 1 December 2000
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 19 (23), 6401-6407
- https://doi.org/10.1093/emboj/19.23.6401
Abstract
In eukaryotic cells, hormones and neurotransmitters that engage the phosphoinositide pathway evoke a biphasic increase in intracellular free Ca2+ concentration: an initial transient release of Ca2+ from intracellular stores is followed by a sustained phase of Ca2+ influx. This influx is generally store dependent. Most attention has focused on the link between the endoplasmic reticulum and store‐operated Ca2+ channels in the plasma membrane. Here, we describe that respiring mitochondria are also essential for the activation of macroscopic store‐operated Ca2+ currents under physiological conditions of weak intracellular Ca2+ buffering. We further show that Ca2+‐dependent slow inactivation of Ca2+ influx, a widespread but poorly understood phenomenon, is regulated by mitochondrial buffering of cytosolic Ca2+. Thus, by enabling macroscopic store‐operated Ca2+ current to activate, and then by controlling its extent and duration, mitochondria play a crucial role in all stages of store‐operated Ca2+ influx. Store‐operated Ca2+ entry reflects a dynamic interplay between endoplasmic reticulum, mitochondria and plasma membrane.Keywords
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