Skip to main content

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

  • Chapter
  • First Online:
Store-operated Ca2+ entry (SOCE) pathways
  • 669 Accesses

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abramov AY, Fraley C, Diao CT, Winkfein R, Colicos MA, Duchen MR, French RJ, Pavlov E (2007) Targeted polyphosphatase expression alters mitochondrial metabolism and inhibits calcium-dependent cell death. Proc Natl Acad Sci USA 104(46):18091–18096

    Article  PubMed  CAS  Google Scholar 

  • Aichberger KJ, Mittermann I, Reininger R, Seiberler S, Swoboda I, Spitzauer S, Kopp T, Stingl G, Sperr WR, Valent P, Repa A, Bohle B, Kraft D, Valenta R (2005) Hom s 4, an IgE-reactive autoantigen belonging to a new subfamily of calcium-binding proteins, can induce Th cell type 1-mediated autoreactivity. J Immunol 175(2):1286–1294

    PubMed  CAS  Google Scholar 

  • Arnaudeau S, Kelley WL, Walsh JV Jr, Demaurex N (2001) Mitochondria recycle Ca2+ to the endoplasmic reticulum and prevent the depletion of neighboring endoplasmic reticulum regions. J Biol Chem 276(31):29430–29439

    Article  PubMed  CAS  Google Scholar 

  • Bernardi P (1999) Mitochondrial transport of cations: channels, exchangers, and permeability transition. Physiol Rev 79(4):1127–1155

    PubMed  CAS  Google Scholar 

  • Berridge MJ, Lipp P, Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1(1):11–21

    Article  PubMed  CAS  Google Scholar 

  • Bolotina VM (2008) Orai, STIM1 and iPLA2beta: a view from a different perspective. J Physiol 586(13):3035–3042

    Article  PubMed  CAS  Google Scholar 

  • Bolotina VM, Csutora P (2005) CIF and other mysteries of the store-operated Ca2+-entry pathway. Trends Biochem Sci 30(7):378–387

    Article  PubMed  CAS  Google Scholar 

  • Bootman MD, Collins TJ, Peppiatt CM, Prothero LS, MacKenzie L, De Smet P, Travers M, Tovey SC, Seo JT, Berridge MJ, Ciccolini F, Lipp P (2001) Calcium signalling–an overview. Semin Cell Dev Biol 12(1):3–10

    Article  PubMed  CAS  Google Scholar 

  • Braschi E, McBride HM (2010) Mitochondria and the culture of the Borg: understanding the integration of mitochondrial function within the reticulum, the cell, and the organism. Bioessays 32(11):958–966

    Article  PubMed  CAS  Google Scholar 

  • Carafoli E (2002) Calcium signaling: a tale for all seasons. Proc Natl Acad Sci USA 99(3):1115–1122

    Article  PubMed  CAS  Google Scholar 

  • Chvanov M, Walsh CM, Haynes LP, Voronina SG, Lur G, Gerasimenko OV, Barraclough R, Rudland PS, Petersen OH, Burgoyne RD, Tepikin AV (2008) ATP depletion induces translocation of STIM1 to puncta and formation of STIM1-ORAI1 clusters: translocation and re-translocation of STIM1 does not require ATP. Pflugers Arch 457(2):505–517

    Article  PubMed  CAS  Google Scholar 

  • Csordas G, Renken C, Varnai P, Walter L, Weaver D, Buttle KF, Balla T, Mannella CA, Hajnoczky G (2006) Structural and functional features and significance of the physical linkage between ER and mitochondria. J Cell Biol 174(7):915–921

    Article  PubMed  CAS  Google Scholar 

  • Csordás G, Várnai P, Golenár T, Roy S, Purkins G, Schneider TG, Balla T, Hajnóczky G (2010) Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface. Mol Cell 39(1):121–132

    Article  PubMed  Google Scholar 

  • de Brito OM, Scorrano L (2008) Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456(7222):605–610

    Article  PubMed  Google Scholar 

  • DeLuca H, Engstrom G (1961) Calcium uptake by rat kidney mitochondria. Proc Natl Acad Sci U S A 47:1744–1750

    Article  PubMed  CAS  Google Scholar 

  • Demaurex N, Poburko D, Frieden M (2009) Regulation of plasma membrane calcium fluxes by mitochondria. Biochim Biophys Acta 1787(11):1383–1394

    Article  PubMed  CAS  Google Scholar 

  • Dolmetsch RE, Xu K, Lewis RS (1998) Calcium oscillations increase the efficiency and specificity of gene expression. Nature 392(6679):933–936

    Article  PubMed  CAS  Google Scholar 

  • Duchen MR, Verkhratsky A, Muallem S (2008) Mitochondria and calcium in health and disease. Cell Calcium 44(1):1–5

    Article  PubMed  CAS  Google Scholar 

  • Feldman B, Fedida-Metula S, Nita J, Sekler I, Fishman D (2010) Coupling of mitochondria to store-operated Ca2 + −signaling sustains constitutive activation of protein kinase B/Akt and augments survival of malignant melanoma cells. Cell Calcium 47(6):525–537

    Article  PubMed  CAS  Google Scholar 

  • Feske S (2007) Calcium signalling in lymphocyte activation and disease. Nat Rev Immunol 7(9):690–702

    Article  PubMed  CAS  Google Scholar 

  • Fomina AF, Nowycky MC (1999) A current activated on depletion of intracellular Ca2+ stores can regulate exocytosis in adrenal chromaffin cells. J Neurosci 19(10):3711–3722

    PubMed  CAS  Google Scholar 

  • Frazier AE, Taylor RD, Mick DU, Warscheid B, Stoepel N, Meyer HE, Ryan MT, Guiard B, Rehling P (2006) Mdm38 interacts with ribosomes and is a component of the mitochondrial protein export machinery. J Cell Biol 172(4):553–564

    Article  PubMed  CAS  Google Scholar 

  • Frieden M, James D, Castelbou C, Danckaert A, Martinou JC, Demaurex N (2004) Ca2+ homeostasis during mitochondrial fragmentation and perinuclear clustering induced by hFis1. J Biol Chem 279(21):22704–22714

    Article  PubMed  CAS  Google Scholar 

  • Frischauf I, Schindl R, Derler I, Bergsmann J, Fahrner M, Romanin C (2008) The STIM/Orai coupling machinery. Channels (Austin) 2(4):261–268

    Article  Google Scholar 

  • Giacomello M, Drago I, Bortolozzi M, Scorzeto M, Gianelle A, Pizzo P, Pozzan T (2010) Ca2+ hot spots on the mitochondrial surface are generated by Ca2+ mobilization from stores, but not by activation of store-operated Ca2+ channels. Mol Cell 38(2):280–290

    Article  PubMed  CAS  Google Scholar 

  • Gilabert JA, Parekh AB (2000) Respiring mitochondria determine the pattern of activation and inactivation of the store-operated Ca2+ current ICRAC. EMBO J 19(23):6401–6407

    Article  PubMed  CAS  Google Scholar 

  • Gilabert JA, Bakowski D, Parekh AB (2001) Energized mitochondria increase the dynamic range over which inositol 1,4,5-trisphosphate activates store-operated calcium influx. EMBO J 20(11):2672–2679

    Article  PubMed  CAS  Google Scholar 

  • Graier WF, Frieden M, Malli R (2007) Mitochondria and Ca2+ signaling: old guests, new functions. Pflugers Arch 455:375–396

    Article  PubMed  CAS  Google Scholar 

  • Graier W, Trenker M, Malli R (2008) Mitochondrial Ca2+, the secret behind the function of uncoupling proteins 2 and 3? Cell Calcium 44:36–50

    Article  PubMed  CAS  Google Scholar 

  • Gunter TE, Sheu S-S (2009) Characteristics and possible functions of mitochondrial Ca2+ transport mechanisms. Biochim Biophys Acta 1787(11):1291–1308

    Article  PubMed  CAS  Google Scholar 

  • Gunter TE, Buntinas L, Sparagna G, Eliseev R, Gunter K (2000) Mitochondrial calcium transport: mechanisms and functions. Cell Calcium 28(5–6):285–296

    Article  PubMed  CAS  Google Scholar 

  • Hajnóczky G, Csordás G (2010) Calcium signalling: fishing out molecules of mitochondrial calcium transport. Curr Biol 20(20):R888–R891

    Article  PubMed  Google Scholar 

  • Hajnoczky G, Hager R, Thomas AP (1999) Mitochondria suppress local feedback activation of inositol 1,4, 5-trisphosphate receptors by Ca2+. J Biol Chem 274(20):14157–14162

    Article  PubMed  CAS  Google Scholar 

  • Hajnoczky G, Csordas G, Das S, Garcia-Perez C, Saotome M, Sinha Roy S, Yi M (2006) Mitochondrial calcium signalling and cell death: approaches for assessing the role of mitochondrial Ca2+ uptake in apoptosis. Cell Calcium 40(5–6):553–560

    Article  PubMed  CAS  Google Scholar 

  • Han X-J, Lu Y-F, Li S-A, Kaitsuka T, Sato Y, Tomizawa K, Nairn AC, Takei K, Matsui H, Matsushita M (2008) CaM kinase I alpha-induced phosphorylation of Drp1 regulates mitochondrial morphology. J Cell Biol 182(3):573–585

    Article  PubMed  CAS  Google Scholar 

  • Hoth M, Fanger CM, Lewis RS (1997) Mitochondrial regulation of store-operated calcium signaling in T lymphocytes. J Cell Biol 137(3):633–648

    Article  PubMed  CAS  Google Scholar 

  • Hoth M, Button DC, Lewis RS (2000) Mitochondrial control of calcium-channel gating: a mechanism for sustained signaling and transcriptional activation in T lymphocytes. Proc Natl Acad Sci U S A 97(19):10607–10612

    Article  PubMed  CAS  Google Scholar 

  • Huberts DHEW, van der Klei IJ (2010) Moonlighting proteins: an intriguing mode of multitasking. Biochim Biophys Acta 1803(4):520–525

    Article  PubMed  CAS  Google Scholar 

  • Jiang D, Zhao L, Clapham DE (2009) Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter. Science 326(5949):144–147

    Article  PubMed  CAS  Google Scholar 

  • Kirichok Y, Krapivinsky G, Clapham DE (2004) The mitochondrial calcium uniporter is a highly selective ion channel. Nature 427(6972):360–364

    Article  PubMed  CAS  Google Scholar 

  • Knot HJ, Laher I, Sobie EA, Guatimosim S, Gomez-Viquez L, Hartmann H, Song LS, Lederer WJ, Graier WF, Malli R, Frieden M, Petersen OH (2005) Twenty years of calcium imaging: cell physiology to dye for. Mol Interv 5(2):112–127

    Article  PubMed  CAS  Google Scholar 

  • KozieÅ‚ K, Lebiedzinska M, Szabadkai G, Onopiuk M, Brutkowski W, Wierzbicka K, WilczyÅ„ski G, Pinton P, DuszyÅ„ski J, ZabÅ‚ocki K, Wieckowski MR (2009) Plasma membrane associated membranes (PAM) from Jurkat cells contain STIM1 protein is PAM involved in the capacitative calcium entry? Int J Biochem Cell Biol 41(12):2440–2449

    Article  PubMed  Google Scholar 

  • Lampe PA, Cornbrooks EB, Juhasz A, Johnson EM, Franklin JL (1995) Suppression of programmed neuronal death by a thapsigargin-induced Ca2+ influx. J Neurobiol 26(2):205–212

    Article  PubMed  CAS  Google Scholar 

  • Lebiedzinska M, Szabadkai G, Jones AWE, Duszynski J, Wieckowski MR (2009) Interactions between the endoplasmic reticulum, mitochondria, plasma membrane and other subcellular organelles. Int J Biochem Cell Biol 41(10):1805–1816

    Article  PubMed  CAS  Google Scholar 

  • Lin S, Fagan KA, Li KX, Shaul PW, Cooper DM, Rodman DM (2000) Sustained endothelial nitric-oxide synthase activation requires capacitative Ca2+ entry. J Biol Chem 275(24):17979–17985

    Article  PubMed  CAS  Google Scholar 

  • Liou J, Kim ML, Heo WD, Jones JT, Myers JW, Ferrell JE Jr, Meyer T (2005) STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr Biol 15(13):1235–1241

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Weaver D, Shirihai O, Hajnóczky G (2009) Mitochondrial ‘kiss-and-run’: interplay between mitochondrial motility and fusion-fission dynamics. EMBO J 28:3074–3089

    Article  PubMed  CAS  Google Scholar 

  • Malli R, Graier WF (2010) Mitochondrial Ca2+ channels: great unknowns with important functions. FEBS Lett 584(10):1942–1947

    Article  PubMed  CAS  Google Scholar 

  • Malli R, Frieden M, Osibow K, Graier WF (2003a) Mitochondria efficiently buffer subplasmalemmal Ca2+ elevation during agonist stimulation. J Biol Chem 278(12):10807–10815

    Article  PubMed  CAS  Google Scholar 

  • Malli R, Frieden M, Osibow K, Zoratti C, Mayer M, Demaurex N, Graier WF (2003b) Sustained Ca2+ transfer across mitochondria is Essential for mitochondrial Ca2+ buffering, sore-operated Ca2+ entry, and Ca2+ store refilling. J Biol Chem 278(45):44769–44779

    Article  PubMed  CAS  Google Scholar 

  • Malli R, Frieden M, Trenker M, Graier WF (2005) The role of mitochondria for Ca2+ refilling of the endoplasmic reticulum. J Biol Chem 280(13):12114–12122

    Article  PubMed  CAS  Google Scholar 

  • Malli R, Naghdi S, Romanin C, Graier WF (2008) Cytosolic Ca2+ prevents the subplasmalemmal clustering of STIM1: an intrinsic mechanism to avoid Ca2+ overload. J Cell Sci 121(Pt 19):3133–3139

    Article  PubMed  CAS  Google Scholar 

  • McBride HM, Neuspiel M, Wasiak S (2006) Mitochondria: more than just a powerhouse. Curr Biol 16(14):R551–R560

    Article  PubMed  CAS  Google Scholar 

  • McFadzean I, Gibson A (2002) The developing relationship between receptor-operated and store-operated calcium channels in smooth muscle. Br J Pharmacol 135(1):1–13

    Article  PubMed  CAS  Google Scholar 

  • Michalak M, Robert Parker JM, Opas M (2002) Ca2+ signaling and calcium binding chaperones of the endoplasmic reticulum. Cell Calcium 32(5–6):269–278

    Article  PubMed  CAS  Google Scholar 

  • Michels G, Khan IF, Endres-Becker J, Rottlaender D, Herzig S, Ruhparwar A, Wahlers T, Hoppe UC (2009) Regulation of the human cardiac mitochondrial Ca2+ uptake by 2 different voltage-gated Ca2+ channels. Circulation 119(18):2435–2443

    Article  PubMed  CAS  Google Scholar 

  • Montalvo GB, Artalejo AR, Gilabert JA (2006) ATP from subplasmalemmal mitochondria controls Ca2+-dependent inactivation of CRAC channels. J Biol Chem 281(47):35616–35623

    Article  PubMed  CAS  Google 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(12):8014–8022

    Article  PubMed  CAS  Google Scholar 

  • Nagai T, Sawano A, Park ES, Miyawaki A (2001) Circularly permuted green fluorescent proteins engineered to sense Ca2+. Proc Natl Acad Sci U S A 98(6):3197–3202

    Article  PubMed  CAS  Google Scholar 

  • Naghdi S, Waldeck-Weiermair M, Fertschai I, Poteser M, Graier WF, Malli R (2010) Mitochondrial Ca2+ uptake and not mitochondrial motility is required for STIM1-Orai1-dependent store-operated Ca2+ entry. J Cell Sci 123:2553–2564

    Article  PubMed  CAS  Google Scholar 

  • Nicholls DG (2005) Mitochondria and calcium signaling. Cell Calcium 38(3–4):311–317

    Article  PubMed  CAS  Google Scholar 

  • Nowikovsky K, Froschauer EM, Zsurka G, Samaj J, Reipert S, Kolisek M, Wiesenberger G, Schweyen RJ (2004) The LETM1/YOL027 gene family encodes a factor of the mitochondrial K+ homeostasis with a potential role in the Wolf-Hirschhorn syndrome. J Biol Chem 279(29):30307–30315

    Article  PubMed  CAS  Google Scholar 

  • Osibow K, Frank S, Malli R, Zechner R, Graier WF (2006) Mitochondria maintain maturation and secretion of lipoprotein lipase in the endoplasmic reticulum. Biochem J 396(1):173–182

    Article  PubMed  CAS  Google Scholar 

  • Parekh AB (1998) Slow feedback inhibition of calcium release-activated calcium current by calcium entry. J Biol Chem 273:14925–14932

    Article  PubMed  CAS  Google Scholar 

  • Parekh AB (2008) Mitochondrial regulation of store-operated CRAC channels. Cell Calcium 44(1):6–13

    Article  PubMed  CAS  Google Scholar 

  • Parekh AB, Putney JW (2005) Store-operated calcium channels. Physiol Rev 85(2):757–810

    Article  PubMed  CAS  Google Scholar 

  • Penna A, Demuro A, Yeromin AV, Zhang SL, Safrina O, Parker I, Cahalan MD (2008) The CRAC channel consists of a tetramer formed by Stim-induced dimerization of Orai dimers. Nature 456(7218):116–120

    Article  PubMed  CAS  Google Scholar 

  • Perocchi F, Gohil VM, Girgis HS, Bao XR, McCombs JE, Palmer AE, Mootha VK (2010) MICU1 encodes a mitochondrial EF hand protein required for Ca2+ uptake. Nature 467(7313):291–296

    Article  PubMed  CAS  Google Scholar 

  • Piao L, Li Y, Kim SJ, Sohn K-C, Yang K-J, Park KA, Byun HS, Won M, Hong J, Hur GM, Seok JH, Shong M, Sack R, Brazil DP, Hemmings BA, Park J (2009) Regulation of OPA1-mediated mitochondrial fusion by leucine zipper/EF-hand-containing transmembrane protein-1 plays a role in apoptosis. Cell Signal 21(5):767–777

    Article  PubMed  CAS  Google Scholar 

  • Potier M, Gonzalez JC, Motiani RK, Abdullaev IF, Bisaillon JM, Singer HA, Trebak M (2009) Evidence for STIM1- and Orai1-dependent store-operated calcium influx through ICRAC in vascular smooth muscle cells: role in proliferation and migration. FASEB J 23(8):2425–2437

    Article  PubMed  CAS  Google Scholar 

  • Putney JW Jr (1986) A model for receptor-regulated calcium entry. Cell Calcium 7(1):1–12

    Article  PubMed  CAS  Google Scholar 

  • Putney JW Jr (1990) Capacitative calcium entry revisited. Cell Calcium 11(10):611–624

    Article  PubMed  CAS  Google Scholar 

  • Putney JW Jr (1991) The capacitative model for receptor-activated calcium entry. Adv Pharmacol 22:251–269

    Article  PubMed  CAS  Google Scholar 

  • Quintana A, Schwindling C, Wenning AS, Becherer U, Rettig J, Schwarz EC, Hoth M (2007) T cell activation requires mitochondrial translocation to the immunological synapse. Proc Natl Acad Sci U S A 104(36):14418–14423

    Article  PubMed  CAS  Google Scholar 

  • Rizzuto R, Simpson AW, Brini M, Pozzan T (1992) Rapid changes of mitochondrial Ca2+ revealed by specifically targeted recombinant aequorin. Nature 358:325–327

    Article  PubMed  CAS  Google Scholar 

  • Rizzuto R, Pinton P, Carrington W, Fay FS, Fogarty KE, Lifshitz LM, Tuft RA, Pozzan T (1998) Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 280(5370):1763–1766

    Article  PubMed  CAS  Google Scholar 

  • Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak JA, Wagner SL, Cahalan MD, Velicelebi G, Stauderman KA (2005) STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol 169(3):435–445

    Article  PubMed  CAS  Google Scholar 

  • Saotome M, Safiulina D, Szabadkai G, Das S, Fransson A, Aspenstrom P, Rizzuto R, Hajnóczky G (2008) Bidirectional Ca2+-dependent control of mitochondrial dynamics by the Miro GTPase. Proc Natl Acad Sci U S A 105(52):20728–20733

    Article  PubMed  CAS  Google Scholar 

  • Scarpa A, Graziotti P (1973) Mechanisms for intracellular calcium regulation in heart. I. Stopped-flow measurements of Ca2+ uptake by cardiac mitochondria. J Gen Physiol 62(6):756–772

    Article  PubMed  CAS  Google Scholar 

  • Singaravelu K, Nelson C, Bakowski D, Martins de Brito O, Ng S-W, Di Capite J, Powell T, Scorrano L, Parekh AB (2011) Mitofusin 2 regulates STIM1 migration from the Ca2+ store to the plasma membrane in cells with depolarised mitochondria. J Biol Chem 286(14):12189–12201

    Article  PubMed  CAS  Google Scholar 

  • Spät A, Szanda G, Csordás G, Hajnóczky G (2008) High- and low-calcium-dependent mechanisms of mitochondrial calcium signalling. Cell Calcium 44:51–63

    Article  PubMed  Google Scholar 

  • Szabadkai G, Duchen MR (2008) Mitochondria: the hub of cellular Ca2+ signaling. Physiology (Bethesda) 23:84–94

    Article  CAS  Google Scholar 

  • Trenker M, Malli R, Fertschai I, Levak-Frank S, Graier WF (2007) Uncoupling proteins 2 and 3 are fundamental for mitochondrial Ca2+ uniport. Nat Cell Biol 9(4):445–452

    Article  PubMed  CAS  Google Scholar 

  • Trenker M, Fertschai I, Malli R, Graier WF (2008) UCP2/3 – likely to be fundamental for mitochondrial Ca2+ uniport. Nat Cell Biol 10(11):1237–1240

    Article  CAS  Google Scholar 

  • Varadi A, Cirulli V, Rutter GA (2004) Mitochondrial localization as a determinant of capacitative Ca2+ entry in HeLa cells. Cell Calcium 36(6):499–508

    Article  PubMed  CAS  Google Scholar 

  • Várnai P, Tóth B, Tóth DJ, Hunyady L, Balla T (2007) Visualization and manipulation of plasma membrane-endoplasmic reticulum contact sites indicates the presence of additional molecular components within the STIM1-Orai1 complex. J Biol Chem 282(40):29678–29690

    Article  PubMed  Google Scholar 

  • Várnai P, Hunyady L, Balla T (2009) STIM and Orai: the long-awaited constituents of store-operated calcium entry. Trends Pharmacol Sci 30(3):118–128

    Article  PubMed  Google Scholar 

  • Vasington FD, Murphy J (1962) Ca2+ ion uptake by rat kidney mitochondria and its dependence on respiration and phosphorylation. J Biol Chem 237:2670–2677

    PubMed  CAS  Google Scholar 

  • Waldeck-Weiermair M, Duan X, Naghdi S, Khan MJ, Trenker M, Malli R, Graier WF (2010a) Uncoupling protein 3 adjusts mitochondrial Ca2+ uptake to high and low Ca2+ signals. Cell Calcium 48:288–301

    Article  PubMed  CAS  Google Scholar 

  • Waldeck-Weiermair M, Malli R, Naghdi S, Trenker M, Kahn MJ, Graier WF (2010b) The contribution of UCP2 and UCP3 to mitochondrial Ca2+ uptake is differentially determined by the source of supplied Ca2+. Cell Calcium 47:433–440

    Article  PubMed  CAS  Google Scholar 

  • Walsh C, Barrow S, Voronina S, Chvanov M, Petersen OH, Tepikin A (2009) Modulation of calcium signalling by mitochondria. Biochim Biophys Acta 1787(11):1374–1382

    Article  PubMed  CAS  Google Scholar 

  • Zhang SL, Yu Y, Roos J, Kozak JA, Deerinck TJ, Ellisman MH, Stauderman KA, Cahalan MD (2005) STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. Nature 437(7060):902–905

    Article  PubMed  CAS  Google Scholar 

  • Zweifach A, Lewis RS (1995) Slow calcium-dependent inactivation of depletion-activated calcium current Store-dependent and -independent mechanisms. J Biol Chem 270(24):14445–14451

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wolfgang F. Graier .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Wien

About this chapter

Cite this chapter

Malli, R., Graier, W.F. (2012). The Role of Mitochondria in the Activation/Maintenance of SOCE. In: Groschner, K., Graier, W., Romanin, C. (eds) Store-operated Ca2+ entry (SOCE) pathways. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0962-5_15

Download citation

Publish with us

Policies and ethics