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Endoplasmic reticulum–mitochondria coupling: local Ca2+ signalling with functional consequences

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Abstract

Plasma membrane store-operated Ca2+ release-activated Ca2+ (CRAC) channels are a widespread and conserved Ca2+ influx pathway, driving activation of a range of spatially and temporally distinct cellular responses. Although CRAC channels are activated by the loss of Ca2+ from the endoplasmic reticulum, their gating is regulated by mitochondria. Through their ability to buffer cytoplasmic Ca2+, mitochondria take up Ca2+ released from the endoplasmic reticulum by InsP3 receptors, leading to more extensive store depletion and stronger activation of CRAC channels. Mitochondria also buffer Ca2+ that enters through CRAC channels, reducing Ca2+-dependent slow inactivation of the channels. In addition, depolarised mitochondria impair movement of the CRAC channel activating protein STIM1 across the endoplasmic reticulum membrane. Because they regulate CRAC channel activity, particularly Ca2+-dependent slow inactivation, mitochondria influence CRAC channel-driven enzyme activation, secretion and gene expression. Mitochondrial regulation of CRAC channels therefore provides an important control element to the regulation of intracellular Ca2+ signalling.

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Acknowledgments

Work in the authors’ laboratory is supported by the Medical Research Council.

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Authors and Affiliations

  1. Department of Physiology, Anatomy and Genetics Sherrington Building, South Parks Road, Oxford, OX1 3PT, UK

    Daniel Bakowski, Charmaine Nelson & Anant B. Parekh

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  1. Daniel Bakowski
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  2. Charmaine Nelson
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  3. Anant B. Parekh
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Correspondence to Anant B. Parekh.

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This article is published as part of the Special Issue on Cell-specific roles of mitochondrial Ca2+ handling.

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Bakowski, D., Nelson, C. & Parekh, A.B. Endoplasmic reticulum–mitochondria coupling: local Ca2+ signalling with functional consequences. Pflugers Arch - Eur J Physiol 464, 27–32 (2012). https://doi.org/10.1007/s00424-012-1095-x

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  • DOI: https://doi.org/10.1007/s00424-012-1095-x

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