Skip to main content
SpringerLink
Log in

Endoplasmic Reticulum-Mitochondria Communication Through Ca2+ Signaling: The Importance of Mitochondria-Associated Membranes (MAMs)

  • Chapter
  • First Online:
Organelle Contact Sites

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 997))

Abstract

The execution of proper Ca2+ signaling requires close apposition between the endoplasmic reticulum (ER) and mitochondria. Hence, Ca2+ released from the ER is “quasi-synaptically” transferred to mitochondrial matrix, where Ca2+ stimulates mitochondrial ATP synthesis by activating the tricarboxylic acid (TCA) cycle. However, when the Ca2+ transfer is excessive and sustained, mitochondrial Ca2+ overload induces apoptosis by opening the mitochondrial permeability transition pore. A large number of regulatory proteins reside at mitochondria-associated ER membranes (MAMs) to maintain the optimal distance between the organelles and to coordinate the functionality of both ER and mitochondrial Ca2+ transporters or channels. In this chapter, we discuss the different pathways involved in the regulation of ER-mitochondria Ca2+ flux and describe the activities of the various Ca2+ players based on their primary intra-organelle localization.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
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

  • Amador FJ, Stathopulos PB, Enomoto M, Ikura M (2013) Ryanodine receptor calcium release channels: lessons from structure-function studies. FEBS J 280:5456–5470

    Article  CAS  PubMed  Google Scholar 

  • Anelli T, Alessio M, Bachi A, Bergamelli L, Bertoli G, Camerini S, Mezghrani A, Ruffato E, Simmen T, Sitia R (2003) Thiol-mediated protein retention in the endoplasmic reticulum: the role of ERp44. EMBO J 22:5015–5022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anelli T, Bergamelli L, Margittai E, Rimessi A, Fagioli C, Malgaroli A, Pinton P, Ripamonti M, Rizzuto R, Sitia R (2012) Ero1α regulates Ca2+ fluxes at the endoplasmic reticulum-mitochondria interface (MAM). Antioxid Redox Signal 16:1077–1087

    Article  CAS  PubMed  Google Scholar 

  • Arasaki K, Shimizu H, Mogari H, Nishida N, Hirota N, Furuno A, Kudo Y, Baba M, Baba N, Cheng J et al (2015) A role for the ancient SNARE syntaxin 17 in regulating mitochondrial division. Dev Cell 32:304–317

    Article  CAS  PubMed  Google Scholar 

  • Arnaudeau S, Frieden M, Nakamura K, Castelbou C, Michalak M, Demaurex N (2002) Calreticulin differentially modulates calcium uptake and release in the endoplasmic reticulum and mitochondria. J Biol Chem 277:46696–46705

    Article  CAS  PubMed  Google Scholar 

  • Arruda AP, Pers BM, Parlakgul G, Guney E, Inouye K, Hotamisligil GS (2014) Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity. Nat Med 20:1427–1435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Asahi M, Nakayama H, Tada M, Otsu K (2003) Regulation of sarco(endo)plasmic reticulum Ca2+ adenosine triphosphatase by phospholamban and sarcolipin: implication for cardiac hypertrophy and failure. Trends Cardiovasc Med 13:152–157

    Article  CAS  PubMed  Google Scholar 

  • Ashby MC, Tepikin AV (2001) ER calcium and the functions of intracellular organelles. Semin Cell Dev Biol 12:11–17

    Article  CAS  PubMed  Google Scholar 

  • Baksh S, Burns K, Andrin C, Michalak M (1995) Interaction of calreticulin with protein disulfide isomerase. J Biol Chem 270:31338–31344

    Article  CAS  PubMed  Google Scholar 

  • Ben-Hail D, Shoshan-Barmatz V (2016) VDAC1-interacting anion transport inhibitors inhibit VDAC1 oligomerization and apoptosis. Biochim Biophys Acta 1863:1612–1623

    Article  CAS  PubMed  Google Scholar 

  • Berridge MJ (2016) The Inositol trisphosphate/calcium signaling pathway in health and disease. Physiol Rev 96:1261–1296

    Article  PubMed  Google Scholar 

  • Betz C, Stracka D, Prescianotto-Baschong C, Frieden M, Demaurex N, Hall MN (2013) Feature Article: mTOR complex 2-Akt signaling at mitochondria-associated endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology. Proc Natl Acad Sci USA 110:12526–12534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bittremieux M, Parys JB, Pinton P, Bultynck G (2016) ER functions of oncogenes and tumor suppressors: Modulators of intracellular Ca2+ signaling. Biochim Biophys Acta 1863:1364–1378

    Article  CAS  PubMed  Google Scholar 

  • Bononi A, Bonora M, Marchi S, Missiroli S, Poletti F, Giorgi C, Pandolfi PP, Pinton P (2013) Identification of PTEN at the ER and MAMs and its regulation of Ca2+ signaling and apoptosis in a protein phosphatase-dependent manner. Cell Death Differ 20:1631–1643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonora M, Patergnani S, Rimessi A, De Marchi E, Suski JM, Bononi A, Giorgi C, Marchi S, Missiroli S, Poletti F et al (2012) ATP synthesis and storage. Purinergic Signal 8:343–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonora M, Giorgi C, Bononi A, Marchi S, Patergnani S, Rimessi A, Rizzuto R, Pinton P (2013) Subcellular calcium measurements in mammalian cells using jellyfish photoprotein aequorin-based probes. Nat Protoc 8:2105–2118

    Article  CAS  PubMed  Google Scholar 

  • Bonora M, Wieckowski MR, Chinopoulos C, Kepp O, Kroemer G, Galluzzi L, Pinton P (2015) Molecular mechanisms of cell death: central implication of ATP synthase in mitochondrial permeability transition. Oncogene 34:1475–1486

    Article  CAS  PubMed  Google Scholar 

  • Bravo R, Vicencio JM, Parra V, Troncoso R, Munoz JP, Bui M, Quiroga C, Rodriguez AE, Verdejo HE, Ferreira J et al (2011) Increased ER-mitochondrial coupling promotes mitochondrial respiration and bioenergetics during early phases of ER stress. J Cell Sci 124:2143–2152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bravo R, Gutierrez T, Paredes F, Gatica D, Rodriguez AE, Pedrozo Z, Chiong M, Parra V, Quest AF, Rothermel BA et al (2012) Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics. Int J Biochem Cell Biol 44:16–20

    Article  CAS  PubMed  Google Scholar 

  • Briggs CA, Chakroborty S, Stutzmann GE (2017) Emerging pathways driving early synaptic pathology in Alzheimer’s disease. Biochem Biophys Res Commun 483(4):988–997

    Google Scholar 

  • Bui M, Gilady SY, Fitzsimmons RE, Benson MD, Lynes EM, Gesson K, Alto NM, Strack S, Scott JD, Simmen T (2010) Rab32 modulates apoptosis onset and mitochondria-associated membrane (MAM) properties. J Biol Chem 285:31590–31602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Camacho P, Lechleiter JD (1995) Calreticulin inhibits repetitive intracellular Ca2+ waves. Cell 82:765–771

    Article  CAS  PubMed  Google Scholar 

  • Cantero-Recasens G, Fandos C, Rubio-Moscardo F, Valverde MA, Vicente R (2010) The asthma-associated ORMDL3 gene product regulates endoplasmic reticulum-mediated calcium signaling and cellular stress. Hum Mol Genet 19:111–121

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Csordas G, Jowdy C, Schneider TG, Csordas N, Wang W, Liu Y, Kohlhaas M, Meiser M, Bergem S et al (2012) Mitofusin 2-containing mitochondrial-reticular microdomains direct rapid cardiomyocyte bioenergetic responses via interorganelle Ca2+ crosstalk. Circ Res 111:863–875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cosson P, Marchetti A, Ravazzola M, Orci L (2012) Mitofusin-2 independent juxtaposition of endoplasmic reticulum and mitochondria: an ultrastructural study. PLoS One 7:e46293

    Article  CAS  PubMed  PubMed Central  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 174:915–921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Csordas G, Varnai P, Golenar T, Roy S, Purkins G, Schneider TG, Balla T, Hajnoczky G (2010) Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface. Mol Cell 39:121–132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Csordas G, Golenar T, Seifert EL, Kamer KJ, Sancak Y, Perocchi F, Moffat C, Weaver D, de la Fuente PS, Bogorad R et al (2013) MICU1 controls both the threshold and cooperative activation of the mitochondrial Ca2+ uniporter. Cell Metab 17:976–987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • De La Fuente S, Fernandez-Sanz C, Vail C, Agra EJ, Holmstrom K, Sun J, Mishra J, Williams D, Finkel T, Murphy E et al (2016) Strategic positioning and biased activity of the mitochondrial calcium uniporter in cardiac muscle. J Biol Chem 291:23343–23362

    Article  CAS  Google Scholar 

  • De Stefani D, Bononi A, Romagnoli A, Messina A, De Pinto V, Pinton P, Rizzuto R (2012) VDAC1 selectively transfers apoptotic Ca2+ signals to mitochondria. Cell Death Differ 19:267–273

    Article  PubMed  CAS  Google Scholar 

  • Decuypere JP, Monaco G, Bultynck G, Missiaen L, De Smedt H, Parys JB (2011) The IP3 receptor-mitochondria connection in apoptosis and autophagy. Biochim Biophys Acta 1813:1003–1013

    Article  CAS  PubMed  Google Scholar 

  • Di Jeso B, Pereira R, Consiglio E, Formisano S, Satrustegui J, Sandoval IV (1998) Demonstration of a Ca2+ requirement for thyroglobulin dimerization and export to the golgi complex. Eur J Biochem 252:583–590

    Article  PubMed  Google Scholar 

  • Di Jeso B, Ulianich L, Pacifico F, Leonardi A, Vito P, Consiglio E, Formisano S, Arvan P (2003) Folding of thyroglobulin in the calnexin/calreticulin pathway and its alteration by loss of Ca2+ from the endoplasmic reticulum. Biochem J 370:449–458

    Article  PubMed  PubMed Central  Google Scholar 

  • Doghman-Bouguerra M, Granatiero V, Sbiera S, Sbiera I, Lacas-Gervais S, Brau F, Fassnacht M, Rizzuto R, Lalli E (2016) FATE1 antagonizes calcium- and drug-induced apoptosis by uncoupling ER and mitochondria. EMBO Rep 17:1264–1280

    Article  CAS  PubMed  Google Scholar 

  • Filadi R, Greotti E, Turacchio G, Luini A, Pozzan T, Pizzo P (2015) Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling. Proc Natl Acad Sci USA 112:E2174–E2181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foskett JK, Philipson B (2015) The mitochondrial Ca2+ uniporter complex. J Mol Cell Cardiol 78:3–8

    Article  CAS  PubMed  Google Scholar 

  • Foskett JK, White C, Cheung KH, Mak DO (2007) Inositol trisphosphate receptor Ca2+ release channels. Physiol Rev 87:593–658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fransson A, Ruusala A, Aspenstrom P (2003) Atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis. J Biol Chem 278:6495–6502

    Article  CAS  PubMed  Google Scholar 

  • Friedman JR, Lackner LL, West M, DiBenedetto JR, Nunnari J, Voeltz GK (2011) ER tubules mark sites of mitochondrial division. Science 334:358–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gerasimenko JV, Sherwood M, Tepikin AV, Petersen OH, Gerasimenko OV (2006) NAADP, cADPR and IP3 all release Ca2+ from the endoplasmic reticulum and an acidic store in the secretory granule area. J Cell Sci 119:226–238

    Article  CAS  PubMed  Google Scholar 

  • Giorgi C, Ito K, Lin HK, Santangelo C, Wieckowski MR, Lebiedzinska M, Bononi A, Bonora M, Duszynski J, Bernardi R et al (2010) PML regulates apoptosis at endoplasmic reticulum by modulating calcium release. Science 330:1247–1251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giorgi C, Baldassari F, Bononi A, Bonora M, De Marchi E, Marchi S, Missiroli S, Patergnani S, Rimessi A, Suski JM et al (2012) Mitochondrial Ca2+ and apoptosis. Cell Calcium 52:36–43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giorgi C, Bonora M, Missiroli S, Poletti F, Ramirez FG, Morciano G, Morganti C, Pandolfi PP, Mammano F, Pinton P (2015a) Intravital imaging reveals p53-dependent cancer cell death induced by phototherapy via calcium signaling. Oncotarget 6:1435–1445

    Article  PubMed  Google Scholar 

  • Giorgi C, Bonora M, Sorrentino G, Missiroli S, Poletti F, Suski JM, Galindo Ramirez F, Rizzuto R, Di Virgilio F, Zito E et al (2015b) p53 at the endoplasmic reticulum regulates apoptosis in a Ca2+-dependent manner. Proc Natl Acad Sci USA 112:1779–1784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giorgi C, Missiroli S, Patergnani S, Duszynski J, Wieckowski MR, Pinton P (2015c) Mitochondria-associated membranes: composition, molecular mechanisms, and physiopathological implications. Antioxid Redox Signal 22:995–1019

    Article  CAS  PubMed  Google Scholar 

  • Glater EE, Megeath LJ, Stowers RS, Schwarz TL (2006) Axonal transport of mitochondria requires milton to recruit kinesin heavy chain and is light chain independent. J Cell Biol 173:545–557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gunter TE, Gunter KK (2001) Uptake of calcium by mitochondria: transport and possible function. IUBMB Life 52:197–204

    Article  CAS  PubMed  Google Scholar 

  • Halestrap AP (2014) The C ring of the F1Fo ATP synthase forms the mitochondrial permeability transition pore: a critical appraisal. Front Oncol 4:234

    Article  PubMed  PubMed Central  Google Scholar 

  • Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A, Fujita N, Oomori H, Noda T, Haraguchi T, Hiraoka Y et al (2013) Autophagosomes form at ER-mitochondria contact sites. Nature 495:389–393

    Article  CAS  PubMed  Google Scholar 

  • Harada M, Luo X, Murohara T, Yang B, Dobrev D, Nattel S (2014) MicroRNA regulation and cardiac calcium signaling: role in cardiac disease and therapeutic potential. Circ Res 114:689–705

    Article  CAS  PubMed  Google Scholar 

  • Haroon S, Vermulst M (2016) Linking mitochondrial dynamics to mitochondrial protein quality control. Curr Opin Genet Dev 38:68–74

    Article  CAS  PubMed  Google Scholar 

  • Hayashi T, Su TP (2007) Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca2+ signaling and cell survival. Cell 131:596–610

    Article  CAS  PubMed  Google Scholar 

  • Higo T, Hattori M, Nakamura T, Natsume T, Michikawa T, Mikoshiba K (2005) Subtype-specific and ER lumenal environment-dependent regulation of inositol 1,4,5-trisphosphate receptor type 1 by ERp44. Cell 120:85–98

    Article  CAS  PubMed  Google Scholar 

  • Hofer AM, Schulz I (1996) Quantification of intraluminal free [Ca] in the agonist-sensitive internal calcium store using compartmentalized fluorescent indicators: some considerations. Cell Calcium 20:235–242

    Article  CAS  PubMed  Google Scholar 

  • Hong Z, Chen KH, Dasgupta A, Potus F, Dunham-Snary K, Bonnet S, Tian L, Fu J, Breuils-Bonnet S, Provencher S et al (2017) miR-138 and miR-25 Downregulate MCU, causing pulmonary arterial Hypertension’s cancer phenotype. Am J Respir Crit Care Med 195(4):515–529

    Google Scholar 

  • Ivanova H, Vervliet T, Missiaen L, Parys JB, De Smedt H, Bultynck G (2014) Inositol 1,4,5-trisphosphate receptor-isoform diversity in cell death and survival. Biochim Biophys Acta 1843:2164–2183

    Article  CAS  PubMed  Google Scholar 

  • Iwasawa R, Mahul-Mellier AL, Datler C, Pazarentzos E, Grimm S (2011) Fis1 and Bap31 bridge the mitochondria-ER interface to establish a platform for apoptosis induction. EMBO J 30:556–568

    Article  CAS  PubMed  Google Scholar 

  • Joiner ML, Koval OM, Li J, He BJ, Allamargot C, Gao Z, Luczak ED, Hall DD, Fink BD, Chen B et al (2012) CaMKII determines mitochondrial stress responses in heart. Nature 491:269–273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jonas EA, Porter GA Jr, Beutner G, Mnatsakanyan N, Alavian KN (2015) Cell death disguised: The mitochondrial permeability transition pore as the c-subunit of the F1Fo ATP synthase. Pharmacol Res 99:382–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamer KJ, Mootha VK (2015) The molecular era of the mitochondrial calcium uniporter. Nat Rev Mol Cell Biol 16:545–553

    Article  CAS  PubMed  Google Scholar 

  • Kang S, Dahl R, Hsieh W, Shin A, Zsebo KM, Buettner C, Hajjar RJ, Lebeche D (2016) Small molecular allosteric activator of the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) attenuates diabetes and metabolic disorders. J Biol Chem 291:5185–5198

    Article  CAS  PubMed  Google Scholar 

  • Khan MT, Wagner L 2nd, Yule DI, Bhanumathy C, Joseph SK (2006) Akt kinase phosphorylation of inositol 1,4,5-trisphosphate receptors. J Biol Chem 281:3731–3737

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Krols M, Bultynck G, Janssens S (2016) ER-Mitochondria contact sites: A new regulator of cellular calcium flux comes into play. J Cell Biol 214:367–370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lamb CA, Yoshimori T, Tooze SA (2013) The autophagosome: origins unknown, biogenesis complex. Nat Rev Mol Cell Biol 14:759–774

    Article  CAS  PubMed  Google Scholar 

  • Lasorsa FM, Pinton P, Palmieri L, Fiermonte G, Rizzuto R, Palmieri F (2003) Recombinant expression of the Ca2+-sensitive aspartate/glutamate carrier increases mitochondrial ATP production in agonist-stimulated Chinese hamster ovary cells. J Biol Chem 278:38686–38692

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Hajnoczky G (2009) Ca2+-dependent regulation of mitochondrial dynamics by the Miro-Milton complex. Int J Biochem Cell Biol 41:1972–1976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lynes EM, Bui M, Yap MC, Benson MD, Schneider B, Ellgaard L, Berthiaume LG, Simmen T (2012) Palmitoylated TMX and calnexin target to the mitochondria-associated membrane. EMBO J 31:457–470

    Article  CAS  PubMed  Google Scholar 

  • Lynes EM, Raturi A, Shenkman M, Ortiz Sandoval C, Yap MC, Wu J, Janowicz A, Myhill N, Benson MD, Campbell RE et al (2013) Palmitoylation is the switch that assigns calnexin to quality control or ER Ca2+ signaling. J Cell Sci 126:3893–3903

    Article  CAS  PubMed  Google Scholar 

  • Lytton J, Westlin M, Hanley MR (1991) Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps. J Biol Chem 266:17067–17071

    CAS  PubMed  Google Scholar 

  • Madreiter-Sokolowski CT, Klec C, Parichatikanond W, Stryeck S, Gottschalk B, Pulido S, Rost R, Eroglu E, Hofmann NA, Bondarenko AI et al (2016) PRMT1-mediated methylation of MICU1 determines the UCP2/3 dependency of mitochondrial Ca2+ uptake in immortalized cells. Nat Commun 7:12897

    Article  PubMed  PubMed Central  Google Scholar 

  • Mallilankaraman K, Cardenas C, Doonan PJ, Chandramoorthy HC, Irrinki KM, Golenar T, Csordas G, Madireddi P, Yang J, Muller M et al (2012a) MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism. Nat Cell Biol 14:1336–1343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mallilankaraman K, Doonan P, Cardenas C, Chandramoorthy HC, Muller M, Miller R, Hoffman NE, Gandhirajan RK, Molgo J, Birnbaum MJ et al (2012b) MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca2+ uptake that regulates cell survival. Cell 151:630–644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marchi S, Pinton P (2014) The mitochondrial calcium uniporter complex: molecular components, structure and physiopathological implications. J Physiol 592:829–839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marchi S, Rimessi A, Giorgi C, Baldini C, Ferroni L, Rizzuto R, Pinton P (2008) Akt kinase reducing endoplasmic reticulum Ca2+ release protects cells from Ca2+-dependent apoptotic stimuli. Biochem Biophys Res Commun 375:501–505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marchi S, Marinello M, Bononi A, Bonora M, Giorgi C, Rimessi A, Pinton P (2012) Selective modulation of subtype III IP3R by Akt regulates ER Ca2+ release and apoptosis. Cell Death Dis 3:e304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marchi S, Lupini L, Patergnani S, Rimessi A, Missiroli S, Bonora M, Bononi A, Corra F, Giorgi C, De Marchi E et al (2013) Downregulation of the mitochondrial calcium uniporter by cancer-related miR-25. Curr Biol 23:58–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marchi S, Patergnani S, Pinton P (2014) The endoplasmic reticulum-mitochondria connection: one touch, multiple functions. Biochimica et biophysica acta 1837:461–469

    Article  CAS  PubMed  Google Scholar 

  • Marino M, Stoilova T, Giorgi C, Bachi A, Cattaneo A, Auricchio A, Pinton P, Zito E (2015) SEPN1, an endoplasmic reticulum-localized selenoprotein linked to skeletal muscle pathology, counteracts hyperoxidation by means of redox-regulating SERCA2 pump activity. Hum Mol Genet 24:1843–1855

    Article  CAS  PubMed  Google Scholar 

  • Matsuzaki H, Fujimoto T, Tanaka M, Shirasawa S (2013) Tespa1 is a novel component of mitochondria-associated endoplasmic reticulum membranes and affects mitochondrial calcium flux. Biochem Biophys Res Commun 433:322–326

    Article  CAS  PubMed  Google Scholar 

  • Melo SF, Barauna VG, Neves VJ, Fernandes T, Lara Lda S, Mazzotti DR, Oliveira EM (2015) Exercise training restores the cardiac microRNA-1 and -214 levels regulating Ca2+ handling after myocardial infarction. BMC Cardiovasc Disord 15:166

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mendes CC, Gomes DA, Thompson M, Souto NC, Goes TS, Goes AM, Rodrigues MA, Gomez MV, Nathanson MH, Leite MF (2005) The type III inositol 1,4,5-trisphosphate receptor preferentially transmits apoptotic Ca2+ signals into mitochondria. J Biol Chem 280:40892–40900

    Article  CAS  PubMed  Google Scholar 

  • Michalak M, Groenendyk J, Szabo E, Gold LI, Opas M (2009) Calreticulin, a multi-process calcium-buffering chaperone of the endoplasmic reticulum. Biochem J 417:651–666

    Article  CAS  PubMed  Google Scholar 

  • Missiroli S, Bonora M, Patergnani S, Poletti F, Perrone M, Gafa R, Magri E, Raimondi A, Lanza G, Tacchetti C et al (2016) PML at mitochondria-associated membranes is critical for the repression of autophagy and cancer development. Cell Rep 16:2415–2427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montero M, Alonso MT, Carnicero E, Cuchillo-Ibanez I, Albillos A, Garcia AG, Garcia-Sancho J, Alvarez J (2000) Chromaffin-cell stimulation triggers fast millimolar mitochondrial Ca2+ transients that modulate secretion. Nat Cell Biol 2:57–61

    Article  CAS  PubMed  Google Scholar 

  • Morciano G, Giorgi C, Bonora M, Punzetti S, Pavasini R, Wieckowski MR, Campo G, Pinton P (2015) Molecular identity of the mitochondrial permeability transition pore and its role in ischemia-reperfusion injury. J Mol Cell Cardiol 78:142–153

    Article  CAS  PubMed  Google Scholar 

  • Myhill N, Lynes EM, Nanji JA, Blagoveshchenskaya AD, Fei H, Carmine Simmen K, Cooper TJ, Thomas G, Simmen T (2008) The subcellular distribution of calnexin is mediated by PACS-2. Mol Biol Cell 19:2777–2788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naghdi S, Hajnoczky G (2016) VDAC2-specific cellular functions and the underlying structure. Biochim Biophys Acta 1863:2503–2514

    Article  CAS  PubMed  Google Scholar 

  • Naon D, Scorrano L (2014) At the right distance: ER-mitochondria juxtaposition in cell life and death. Biochim Biophys Acta 1843:2184–2194

    Article  CAS  PubMed  Google Scholar 

  • Naon D, Zaninello M, Giacomello M, Varanita T, Grespi F, Lakshminaranayan S, Serafini A, Semenzato M, Herkenne S, Hernandez-Alvarez MI et al (2016) Critical reappraisal confirms that Mitofusin 2 is an endoplasmic reticulum-mitochondria tether. Proc Natl Acad Sci USA 113:11249–11254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O-Uchi J, Jhun BS, Xu S, Hurst S, Raffaello A, Liu X, Yi B, Zhang H, Gross P, Mishra J et al (2014) Adrenergic signaling regulates mitochondrial Ca2+ uptake through Pyk2-dependent tyrosine phosphorylation of the mitochondrial Ca2+ uniporter. Antioxid Redox Signal 21:863–879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paillusson S, Stoica R, Gomez-Suaga P, Lau DH, Mueller S, Miller T, Miller CC (2016) There’s something wrong with my MAM; the ER-mitochondria axis and neurodegenerative diseases. Trends Neurosci 39:146–157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pan L, Huang BJ, Ma XE, Wang SY, Feng J, Lv F, Liu Y, Li CM, Liang DD, Li J et al (2015) MiR-25 protects cardiomyocytes against oxidative damage by targeting the mitochondrial calcium uniporter. Int J Mol Sci 16:5420–5433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Papp B, Brouland JP, Arbabian A, Gelebart P, Kovacs T, Bobe R, Enouf J, Varin-Blank N, Apati A (2012) Endoplasmic reticulum calcium pumps and cancer cell differentiation. Biomolecules 2:165–186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parys JB, De Smedt H (2012) Inositol 1,4,5-trisphosphate and its receptors. Adv Exp Med Biol 740:255–279

    Article  CAS  PubMed  Google Scholar 

  • Patergnani S, Suski JM, Agnoletto C, Bononi A, Bonora M, De Marchi E, Giorgi C, Marchi S, Missiroli S, Poletti F et al (2011) Calcium signaling around Mitochondria Associated Membranes (MAMs). Cell Commun Signal 9:19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patergnani S, Missiroli S, Marchi S, Giorgi C (2015) Mitochondria-associated endoplasmic reticulum membranes microenvironment: targeting autophagic and apoptotic pathways in cancer therapy. Frontiers in oncology 5:173

    Article  PubMed  PubMed Central  Google Scholar 

  • Patron M, Raffaello A, Granatiero V, Tosatto A, Merli G, De Stefani D, Wright L, Pallafacchina G, Terrin A, Mammucari C et al (2013) The mitochondrial calcium uniporter (MCU): molecular identity and physiological roles. J Biol Chem 288:10750–10758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patron M, Checchetto V, Raffaello A, Teardo E, Vecellio Reane D, Mantoan M, Granatiero V, Szabo I, De Stefani D, Rizzuto R (2014) MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity. Mol Cell 53:726–737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paupe V, Prudent J, Dassa EP, Rendon OZ, Shoubridge EA (2015) CCDC90A (MCUR1) is a cytochrome c oxidase assembly factor and not a regulator of the mitochondrial calcium uniporter. Cell Metab 21:109–116

    Article  CAS  PubMed  Google Scholar 

  • Pinton P, Leo S, Wieckowski MR, Di Benedetto G, Rizzuto R (2004) Long-term modulation of mitochondrial Ca2+ signals by protein kinase C isozymes. J Cell Biol 165:223–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pinton P, Rimessi A, Marchi S, Orsini F, Migliaccio E, Giorgio M, Contursi C, Minucci S, Mantovani F, Wieckowski MR et al (2007) Protein kinase C β and prolyl isomerase 1 regulate mitochondrial effects of the life-span determinant p66Shc. Science 315:659–663

    Article  CAS  PubMed  Google Scholar 

  • Popugaeva E, Pchitskaya E, Bezprozvanny I (2017) Dysregulation of neuronal calcium homeostasis in Alzheimer’s disease – A therapeutic opportunity? Biochem Biophys Res Commun 483(4):998–1004

    Google Scholar 

  • Poston CN, Krishnan SC, Bazemore-Walker CR (2013) In-depth proteomic analysis of mammalian mitochondria-associated membranes (MAM). J Proteomics 79:219–230

    Article  CAS  PubMed  Google Scholar 

  • Prakriya M, Lewis RS (2015) Store-Operated Calcium Channels. Physiol Rev 95:1383–1436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qi H, Li L, Shuai J (2015) Optimal microdomain crosstalk between endoplasmic reticulum and mitochondria for Ca2+ oscillations. Sci Rep 5:7984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raffaello A, De Stefani D, Sabbadin D, Teardo E, Merli G, Picard A, Checchetto V, Moro S, Szabo I, Rizzuto R (2013) The mitochondrial calcium uniporter is a multimer that can include a dominant-negative pore-forming subunit. EMBO J 32:2362–2376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raffaello A, Mammucari C, Gherardi G, Rizzuto R (2016) Calcium at the center of cell signaling: interplay between endoplasmic reticulum, mitochondria, and lysosomes. Trends Biochem Sci 41(12):1035–1049

    Google 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 Cell Biol 159:613–624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raturi A, Gutierrez T, Ortiz-Sandoval C, Ruangkittisakul A, Herrera-Cruz MS, Rockley JP, Gesson K, Ourdev D, Lou PH, Lucchinetti E et al (2016) TMX1 determines cancer cell metabolism as a thiol-based modulator of ER-mitochondria Ca2+ flux. J Cell Biol 214:433–444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ribeiro CM, McKay RR, Hosoki E, Bird GS, Putney JW Jr (2000) Effects of elevated cytoplasmic calcium and protein kinase C on endoplasmic reticulum structure and function in HEK293 cells. Cell Calcium 27:175–185

    Article  CAS  PubMed  Google Scholar 

  • Rimessi A, Giorgi C, Pinton P, Rizzuto R (2008) The versatility of mitochondrial calcium signals: from stimulation of cell metabolism to induction of cell death. Biochim Biophys Acta 1777:808–816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rimessi A, Marchi S, Patergnani S, Pinton P (2014) H-Ras-driven tumoral maintenance is sustained through caveolin-1-dependent alterations in calcium signaling. Oncogene 33:2329–2340

    Article  CAS  PubMed  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 280:1763–1766

    Article  CAS  PubMed  Google Scholar 

  • Rizzuto R, De Stefani D, Raffaello A, Mammucari C (2012) Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol 13:566–578

    Article  CAS  PubMed  Google Scholar 

  • Roderick HL, Lechleiter JD, Camacho P (2000) Cytosolic phosphorylation of calnexin controls intracellular Ca2+ oscillations via an interaction with SERCA2b. J Cell Biol 149:1235–1248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rowland AA, Voeltz GK (2012) Endoplasmic reticulum-mitochondria contacts: function of the junction. Nat Rev Mol Cell Biol 13:607–625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sala-Vila A, Navarro-Lerida I, Sanchez-Alvarez M, Bosch M, Calvo C, Lopez JA, Calvo E, Ferguson C, Giacomello M, Serafini A et al (2016) Interplay between hepatic mitochondria-associated membranes, lipid metabolism and caveolin-1 in mice. Sci Rep 6:27351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sancak Y, Markhard AL, Kitami T, Kovacs-Bogdan E, Kamer KJ, Udeshi ND, Carr SA, Chaudhuri D, Clapham DE, Li AA et al (2013) EMRE is an essential component of the mitochondrial calcium uniporter complex. Science 342:1379–1382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schneeberger M, Dietrich MO, Sebastian D, Imbernon M, Castano C, Garcia A, Esteban Y, Gonzalez-Franquesa A, Rodriguez IC, Bortolozzi A et al (2013) Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance. Cell 155:172–187

    Article  CAS  PubMed  Google Scholar 

  • Sebastian D, Hernandez-Alvarez MI, Segales J, Sorianello E, Munoz JP, Sala D, Waget A, Liesa M, Paz JC, Gopalacharyulu P et al (2012) Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis. Proc Natl Acad Sci USA 109:5523–5528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimizu H, Schredelseker J, Huang J, Lu K, Naghdi S, Lu F, Franklin S, Fiji HD, Wang K, Zhu H et al (2015) Mitochondrial Ca2+ uptake by the voltage-dependent anion channel 2 regulates cardiac rhythmicity. Elife 4:4e0481

    Article  CAS  Google Scholar 

  • Smirnova E, Griparic L, Shurland DL, van der Bliek AM (2001) Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol Biol Cell 12:2245–2256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sugiura A, Nagashima S, Tokuyama T, Amo T, Matsuki Y, Ishido S, Kudo Y, McBride HM, Fukuda T, Matsushita N et al (2013) MITOL regulates endoplasmic reticulum-mitochondria contacts via Mitofusin2. Mol Cell 51:20–34

    Article  CAS  PubMed  Google Scholar 

  • Szabadkai G, Bianchi K, Varnai P, De Stefani D, Wieckowski MR, Cavagna D, Nagy AI, Balla T, Rizzuto R (2006) Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. J Cell Biol 175:901–911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Szado T, Vanderheyden V, Parys JB, De Smedt H, Rietdorf K, Kotelevets L, Chastre E, Khan F, Landegren U, Soderberg O et al (2008) Phosphorylation of inositol 1,4,5-trisphosphate receptors by protein kinase B/Akt inhibits Ca2+ release and apoptosis. Proc Natl Acad Sci USA 105:2427–2432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Terasaki M, Jaffe LA, Hunnicutt GR, Hammer JA 3rd (1996) Structural change of the endoplasmic reticulum during fertilization: evidence for loss of membrane continuity using the green fluorescent protein. Dev Biol 179:320–328

    Article  CAS  PubMed  Google Scholar 

  • Tomar D, Dong Z, Shanmughapriya S, Koch DA, Thomas T, Hoffman NE, Timbalia SA, Goldman SJ, Breves SL, Corbally DP et al (2016) MCUR1 Is a scaffold factor for the MCU complex function and promotes mitochondrial bioenergetics. Cell Rep 15:1673–1685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tooze SA, Jefferies HB, Kalie E, Longatti A, McAlpine FE, McKnight NC, Orsi A, Polson HE, Razi M, Robinson DJ et al (2010) Trafficking and signaling in mammalian autophagy. IUBMB Life 62:503–508

    Article  CAS  PubMed  Google Scholar 

  • Tsai MF, Phillips CB, Ranaghan M, Tsai CW, Wu Y, Willliams C, Miller C (2016) Dual functions of a small regulatory subunit in the mitochondrial calcium uniporter complex. Elife 5:e15545

    PubMed  PubMed Central  Google Scholar 

  • Tubbs E, Theurey P, Vial G, Bendridi N, Bravard A, Chauvin MA, Ji-Cao J, Zoulim F, Bartosch B, Ovize M et al (2014) Mitochondria-associated endoplasmic reticulum membrane (MAM) integrity is required for insulin signaling and is implicated in hepatic insulin resistance. Diabetes 63:3279–3294

    Article  CAS  PubMed  Google Scholar 

  • Vais H, Tanis JE, Muller M, Payne R, Mallilankaraman K, Foskett JK (2015) MCUR1, CCDC90A, is a regulator of the mitochondrial calcium uniporter. Cell Metab 22:533–535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van Petegem F (2012) Ryanodine receptors: structure and function. J Biol Chem 287:31624–31632

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Van Petegem F (2015) Ryanodine receptors: allosteric ion channel giants. J Mol Biol 427:31–53

    Article  PubMed  CAS  Google Scholar 

  • Vance JE (1990) Phospholipid synthesis in a membrane fraction associated with mitochondria. J Biol Chem 265:7248–7256

    CAS  PubMed  Google Scholar 

  • Vance JE (2014) MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond. Biochimica et biophysica acta 1841:595–609

    Article  CAS  PubMed  Google Scholar 

  • Vandecaetsbeek I, Vangheluwe P, Raeymaekers L, Wuytack F, Vanoevelen J (2011) The Ca2+ pumps of the endoplasmic reticulum and Golgi apparatus. Cold Spring Harb Perspect Biol 3

    Google Scholar 

  • Vangheluwe P, Sepulveda MR, Missiaen L, Raeymaekers L, Wuytack F, Vanoevelen J (2009) Intracellular Ca2+- and Mn2+-transport ATPases. Chem Rev 109:4733–4759

    Article  CAS  PubMed  Google Scholar 

  • Verfaillie T, Rubio N, Garg AD, Bultynck G, Rizzuto R, Decuypere JP, Piette J, Linehan C, Gupta S, Samali A et al (2012) PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress. Cell Death Differ 19:1880–1891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vermassen E, Parys JB, Mauger JP (2004) Subcellular distribution of the inositol 1,4,5-trisphosphate receptors: functional relevance and molecular determinants. Biol Cell 96:3–17

    Article  CAS  PubMed  Google Scholar 

  • Vittorini S, Storti S, Parri MS, Cerillo AG, Clerico A (2007) SERCA2a, phospholamban, sarcolipin, and ryanodine receptors gene expression in children with congenital heart defects. Mol Med 13:105–111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wahl M, Sleight RG, Gruenstein E (1992) Association of cytoplasmic free Ca2+ gradients with subcellular organelles. J Cell Physiol 150:593–609

    Article  CAS  PubMed  Google Scholar 

  • Wieckowski MR, Giorgi C, Lebiedzinska M, Duszynski J, Pinton P (2009) Isolation of mitochondria-associated membranes and mitochondria from animal tissues and cells. Nat Protoc 4:1582–1590

    Article  CAS  PubMed  Google Scholar 

  • Zhang A, Williamson CD, Wong DS, Bullough MD, Brown KJ, Hathout Y, Colberg-Poley AM (2011a) Quantitative proteomic analyses of human cytomegalovirus-induced restructuring of endoplasmic reticulum-mitochondrial contacts at late times of infection. Mol Cell Proteomics 10(M111):009936

    PubMed  Google Scholar 

  • Zhang L, Liu Y, Song F, Zheng H, Hu L, Lu H, Liu P, Hao X, Zhang W, Chen K (2011b) Functional SNP in the microRNA-367 binding site in the 3’UTR of the calcium channel ryanodine receptor gene 3 (RYR3) affects breast cancer risk and calcification. Proc Natl Acad Sci USA 108:13653–13658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

P.P. is grateful to Camilla degli Scrovegni for continuous support. P.P. is supported by: Telethon (GGP15219/B), the Italian Association for Cancer Research (AIRC) (IG-18624), the Italian Cystic Fibrosis Research Foundation (19/2014), the Italian Ministry of Education, University and Research (COFIN no. 20129JLHSY_002, FIRB no. RBAP11FXBC_002, and Futuro in Ricerca no. RBFR10EGVP_001), local funds from the University of Ferrara and the Italian Ministry of Health. C.G is supported by AIRC (MFAG-13521), the Italian Ministry of Health, Cariplo and local funds from the University of Ferrara. S.P. is supported by a research fellowship FISM—Fondazione Italiana Sclerosi Multipla—cod. 2014/B/3. GB and JBP are supported by grants from the Research Foundation - Flanders (FWO) (grants G.0571.12N, G.0819.13N, G.0C91.14N, G.0927.15N and G.0A34.16N) and the Research Council - KU Leuven (OT14/101). MB and MK are holders of a Ph.D. Fellowship from the FWO.

Author information

Authors and Affiliations

  1. Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy

    Saverio Marchi, Sonia Missiroli, Claudia Morganti, Simone Patergnani, Luigi Sbano, Alessandro Rimessi, Carlotta Giorgi & Paolo Pinton

  2. Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine and Leuven Kanker Instituut, KU Leuven, Campus Gasthuisberg O&N-I box 802, Herestraat 49, B-3000, Leuven, Belgium

    Mart Bittremieux, Martijn Kerkhofs, Jan B. Parys & Geert Bultynck

Authors
  1. Saverio Marchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mart Bittremieux
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sonia Missiroli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claudia Morganti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Simone Patergnani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luigi Sbano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alessandro Rimessi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Martijn Kerkhofs
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jan B. Parys
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Geert Bultynck
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Carlotta Giorgi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Paolo Pinton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Carlotta Giorgi or Paolo Pinton .

Editor information

Editors and Affiliations

  1. School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan

    Mitsuo Tagaya

  2. Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada

    Thomas Simmen

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Cite this chapter

Marchi, S. et al. (2017). Endoplasmic Reticulum-Mitochondria Communication Through Ca2+ Signaling: The Importance of Mitochondria-Associated Membranes (MAMs). In: Tagaya, M., Simmen, T. (eds) Organelle Contact Sites. Advances in Experimental Medicine and Biology, vol 997. Springer, Singapore. https://doi.org/10.1007/978-981-10-4567-7_4

Download citation

Publish with us

Policies and ethics

Search

Navigation