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The Role of Mitochondria in the Activation/Maintenance of SOCE: The Contribution of Mitochondrial Ca2+ Uptake, Mitochondrial Motility, and Location to Store-Operated Ca2+ Entry

  • Roland Malli
  • Wolfgang F. Graier
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 993)

Abstract

In most cell types, the depletion of internal Ca2+ stores triggers the activation of Ca2+ entry. This crucial phenomenon is known since the 1980s and referred to as store-operated Ca2+ entry (SOCE). With the discoveries of the stromal-interacting molecules (STIMs) and the Ca2+-permeable Orai channels as the long-awaited molecular constituents of SOCE, the role of mitochondria in controlling the activity of this particular Ca2+ entry pathway is kind of buried in oblivion. However, the capability of mitochondria to locally sequester Ca2+ at sites of Ca2+ release and entry was initially supposed to rule SOCE by facilitating the Ca2+ depletion of the endoplasmic reticulum and removing entering Ca2+ from the Ca2+-inhibitable channels, respectively. Moreover, the central role of these organelles in controlling the cellular energy metabolism has been linked to the activity of SOCE. Nevertheless, the exact molecular mechanisms by which mitochondria actually determine SOCE are still pretty obscure. In this essay we describe the complexity of the mitochondrial Ca2+ uptake machinery and its regulation, molecular components, and properties, which open new ways for scrutinizing the contribution of mitochondria to SOCE. Moreover, data concerning the variability of the morphology and cellular distribution of mitochondria as putative determinants of SOCE activation, maintenance, and termination are summarized.

Keywords

Mitochondria Endothelial nitric oxide synthase Ca2+ signaling Store-operated Ca2+ entry Mitochondrial Ca2+ uptake Uncoupling protein 2 MICU1 MCU Protein methylation 

Notes

Acknowledgments

The authors thank Karin Osibow for helpful comments and proofreading. Markus Waldeck-Weiermair provided data regarding the impact of Ca2+ on mitochondrial motility. The laboratory of WF Graier and R Malli is supported by the Austrian Science Funds, FWF (DKplus W 1226-B18 and P 28529-B27). Microscopic equipment is part of the Nikon Center of Excellence, Graz, that is supported by the Austrian infrastructure program 2013/2014, Nikon Austria Inc., and BioTechMed.

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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Institute of Molecular Biology and BiochemistryMedical University of GrazGrazAustria

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