The role of mitochondria in the activation/maintenance of SOCE the contribution of distinct mitochondrial Ca2+ uptake mechanisms, mitochondrial motility and location to store-operated Ca2+ entry

Abstract

In most cell types the depletion of internal Ca2+ stores triggers the activation of Ca2+ entry. This crucial phenomenon is known since the 1980ies and referred to as store-operated Ca2+ entry (SOCE). With recent discoveries of the stromal interacting molecules (STIMs) and Orais 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 distinct mitochondrial Ca2+ uptake machineries, their molecular components and properties, which open new ways for scrutinizing the contribution of mitochondria to SOCE. Moreover, recent data concerning the variability of the morphology and cellular distribution of mitochondria as putative determinants of SOCE activation, maintenance and termination are summarized.