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The Role of Mitochondria in the Activation/Maintenance of SOCE: Membrane Contact Sites as Signaling Hubs Sustaining Store-Operated Ca2+ Entry

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Store-Operated Ca²⁺ Entry (SOCE) Pathways

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 993))

Abstract

Store-operated Ca2+ entry (SOCE) is a cell signaling pathway essential for immune and muscle function controlled by dynamic interactions between Ca2+-sensing STIM proteins on the endoplasmic reticulum (ER) and Ca2+-permeable ORAI channels on the plasma membrane (PM). STIM-ORAI interactions occur at membrane contact sites (MCS), evolutionarily conserved cellular structures characterized by the close apposition (10–20 nm) between the ER and target membranes that facilitate the exchange of lipids by non-vesicular transport mechanisms. STIM-ORAI interactions were considered to be restricted to ER-PM MCS, but recent evidence indicates that productive interactions take place between ER-bound STIM1 and Ca2+ channels located in intracellular organelles. Interactions between the ER and endosomes or lysosomes regulate the lipid homeostasis of these organelles and the propagation of Ca2+ signals initiated by the release of Ca2+ from acidic stores. Intracellular MCS also regulate the efficiency of phagocytosis, a fundamental cellular process essential for immunity and tissue homeostasis, by ensuring the coordinated opening of Ca2+ channels on phagocytic vacuoles and of Ca2+ release channels on juxtaposed ER stores. In this chapter, we review the current knowledge on the molecular composition and architecture of membrane contact sites that sustain Ca2+ signals at the plasma membrane and in intracellular organelles.

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Demaurex, N., Guido, D. (2017). The Role of Mitochondria in the Activation/Maintenance of SOCE: Membrane Contact Sites as Signaling Hubs Sustaining Store-Operated Ca2+ Entry. In: Groschner, K., Graier, W., Romanin, C. (eds) Store-Operated Ca²⁺ Entry (SOCE) Pathways. Advances in Experimental Medicine and Biology, vol 993. Springer, Cham. https://doi.org/10.1007/978-3-319-57732-6_15

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