The Role of Mitochondria in the Activation/Maintenance of SOCE: Store-Operated Ca2+ Entry and Mitochondria
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Mitochondria extensively modify virtually all cellular Ca2+ transport processes, and store-operated Ca2+ entry (SOCE) is no exception to this rule. The interaction between SOCE and mitochondria is complex and reciprocal, substantially altering and, ultimately, fine-tuning both capacitative Ca2+ influx and mitochondrial function. Mitochondria, owing to their considerable Ca2+ accumulation ability, extensively buffer the cytosolic Ca2+ in their vicinity. In turn, the accumulated ion is released back into the neighboring cytosol during net Ca2+ efflux. Since store depletion itself and the successive SOCE are both Ca2+-regulated phenomena, mitochondrial Ca2+ handling may have wide-ranging effects on capacitative Ca2+ influx at any given time. In addition, mitochondria may also produce or consume soluble factors known to affect store-operated channels. On the other hand, Ca2+ entering the cell during SOCE is sensed by mitochondria, and the ensuing mitochondrial Ca2+ uptake boosts mitochondrial energy metabolism and, if Ca2+ overload occurs, may even lead to apoptosis or cell death. In several cell types, mitochondria seem to be sterically excluded from the confined space that forms between the plasma membrane (PM) and endoplasmic reticulum (ER) during SOCE. This implies that high-Ca2+ microdomains comparable to those observed between the ER and mitochondria do not form here. In the following chapter, the above aspects of the many-sided SOCE-mitochondrion interplay will be discussed in greater detail.
KeywordsStore-operated Ca2+ entry Mitochondria Ca2+ uptake Ca2+ release Microdomains NAD(P)H Membrane potential
G. Szanda was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences.
- Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, Koteliansky V, Mootha VK (2011) Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476:341–345PubMedPubMedCentralCrossRefGoogle Scholar
- Csordas G, Golenar T, Seifert EL, Kamer KJ, Sancak Y, Perocchi F, Moffat C, Weaver D, de la Fuente Perez S, Bogorad R, Koteliansky V, Adijanto J, Mootha VK, Hajnoczky G (2013) MICU1 controls both the threshold and cooperative activation of the mitochondrial Ca(2)(+) uniporter. Cell Metab 17:976–987PubMedPubMedCentralCrossRefGoogle Scholar
- Mallilankaraman K, Cardenas C, Doonan PJ, Chandramoorthy HC, Irrinki KM, Golenar T, Csordas G, Madireddi P, Yang J, Muller M, Miller R, Kolesar JE, Molgo J, Kaufman B, Hajnoczky G, Foskett JK, Madesh M (2012a) MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism. Nat Cell Biol 14:1336–1343PubMedPubMedCentralCrossRefGoogle Scholar
- Mallilankaraman K, Doonan P, Cardenas C, Chandramoorthy HC, Muller M, Miller R, Hoffman NE, Gandhirajan RK, Molgo J, Birnbaum MJ, Rothberg BS, Mak DO, Foskett JK, Madesh M (2012b) MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca2+ uptake that regulates cell survival. Cell 151:630–644PubMedPubMedCentralCrossRefGoogle Scholar
- Muik M, Frischauf I, Derler I, Fahrner M, Bergsmann J, Eder P, Schindl R, Hesch C, Polzinger B, Fritsch R, Kahr H, Madl J, Gruber H, Groschner K, Romanin C (2008) Dynamic coupling of the putative coiled-coil domain of ORAI1 with STIM1 mediates ORAI1 channel activation. J Biol Chem 283:8014–8022PubMedCrossRefGoogle Scholar
- Plovanich M, Bogorad RL, Sancak Y, Kamer KJ, Strittmatter L, Li AA, Girgis HS, Kuchimanchi S, De GJ, Speciner L, Taneja N, Oshea J, Koteliansky V, Mootha VK (2013) MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling. PLoS One 8:e55785PubMedPubMedCentralCrossRefGoogle Scholar
- Rao W, Zhang L, Peng C, Hui H, Wang K, Su N, Wang L, Dai SH, Yang YF, Chen T, Luo P, Fei Z (2015) Downregulation of STIM2 improves neuronal survival after traumatic brain injury by alleviating calcium overload and mitochondrial dysfunction. Biochim Biophys Acta 1852:2402–2413PubMedCrossRefGoogle Scholar
- Rapizzi E, Pinton P, Szabadkai G, Wieckowski MR, Vandecasteele G, Baird G, Tuft RA, Fogarty KE, Rizzuto R (2002) Recombinant expression of the voltage-dependent anion channel enhances the transfer of Ca2+ microdomains to mitochondria. J Biol Chem 159:613–624Google Scholar
- Spät A, Hunyady L, Szanda G (2016) Signaling interactions in the adrenal cortex. Front Endocrinol (Lausanne) 7:17Google Scholar
- Tinel H, Cancela JM, Mogami H, Gerasimenko JV, Gerasimenko OV, Tepikin AV, Petersen OH (1999) Active mitochondria surrounding the pancreatic acinar granule region prevent spreading of inositol trisphosphate-evoked local cytosolic Ca2+ signals. EMBO J 18:4999–5008PubMedPubMedCentralCrossRefGoogle Scholar