Abstract
The endoplasmic reticulum (ER) has two important biological functions: protein folding and storing intracellular Ca2+. Importantly, adequate ER Ca2+-store filling is critical for proper protein folding. In many occasions, ER stress is tightly linked to disruption of ER Ca2+ homeostasis, causing the activation of an integrated signaling pathway, the unfolded protein response (UPR). In this book chapter, we will review the ER as a dynamic intracellular Ca2+-storage organelle in a constant state of Ca2+flux that is in close proximity to the mitochondria, thereby controlling cell survival, adaptive responses to stress and apoptosis. Next, we will discuss how altered [Ca2+]ER homeostasis leads to ER stress, and how ER stress and their sensors alters Ca2+ flux. Recent studies provided novel insights in the molecular mechanisms underlying these processes, including a dynamic regulation of ER Ca2+-uptake and –release mechanisms by ER chaperones and the main controller of the ER-stress sensors, GRP78/BiP. Furthermore, recently identified Ca2+-transport systems also seem to target ER-stress proteins. Overall, it is clear that altered Ca2+ signaling and UPR during ER stress are closely related through dynamic physical interactions between their key players.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
Abbreviations
- BI1:
-
Bax inhibitor-1
- BiP:
-
Immunoglobulin heavy chain binding protein
- CaMKII:
-
Calmodulin-dependent protein kinase II
- cyt c:
-
Cytochrome c
- eIF2α:
-
Eukaryotic initiation factor 2α
- ER:
-
Endoplasmic reticulum
- ERAD:
-
ER-associated degradation
- ERO1α:
-
ER oxidoreductin 1α
- FAD:
-
Familial Alzheimers disease
- GRP:
-
Glucose-regulated protein
- HO-1:
-
Heme oxygenase 1
- IMM:
-
Inner mitochondrial membrane
- IP3 :
-
Inositol 1,4,5-trisphosphate
- IP3Rs:
-
Inositol 1,4,5-trisphosphate receptors
- JNK:
-
C-Jun N-terminal kinase
- MAMs:
-
mitochondria associated membranes
- MCU:
-
Mitochondrial Ca2+ uniporter
- mTOR:
-
Mammalian target of rapamycin
- NPR:
-
NADPH-P450 reductase
- OMM:
-
Outer mitochondrial membrane
- P450:
-
Cytochrome P450
- PDI:
-
Protein disulfide isomerase
- PLC:
-
Phospholipase C
- PML:
-
Promyelocytic leukemia
- PTP:
-
Permeability transition pore
- ROS:
-
Reactive oxygen species
- RyRs:
-
Ryanodine receptors
- SERCA:
-
Sarco- and endoplasmic reticulum Ca2+ ATPase
- SERCA1Â T:
-
Truncated sarco- and endoplasmic reticulum Ca2+ ATPase 1
- SPCA1:
-
Secretory pathway Ca2+ ATPase 1
- STIM:
-
Stromal interaction molecule
- TRP:
-
Transient receptor potential
- TRPC6:
-
Canonical transient receptor potential-6
- UPR:
-
Unfolded protein response
- VDAC:
-
Voltage dependant anion channel
References
Berridge MJ, Bootman MD, Roderick HL (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4(7): 517–529
Harr MW, Distelhorst CW (2010) Apoptosis and autophagy: decoding calcium signals that mediate life or death. Cold Spring Harb Perspect Biol. 2(10):a005579
Decuypere JP, Monaco G, Bultynck G, Missiaen L, Smedt H De, Parys JB (2011) The IP3 receptor-mitochondria connection in apoptosis and autophagy. Biochim Biophys Acta 1813(5):1003–1013
Mekahli D, Bultynck G, Parys JB, Smedt H De, Missiaen L (2011) Endoplasmic-reticulum calcium depletion and disease. Cold Spring Harb Perspect Biol 3(6):a004
Berridge MJ (2002) The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium 32(5–6):235–249
Sammels E, Parys JB, Missiaen L, Smedt H De, Bultynck G (2010) Intracellular Ca2+ storage in health and disease: a dynamic equilibrium. Cell Calcium 47(4):297–314
Prins D, Michalak M (2011) Organellar calcium buffers. Cold Spring Harb Perspect Biol 3(3)
Meldolesi J, Pozzan T (1998) The endoplasmic reticulum Ca2+ store: a view from the lumen. Trends Biochem Sci 23(1):10–14
Coe H, Michalak M (2009) Calcium binding chaperones of the endoplasmic reticulum. Gen Physiol Biophys 28 Spec No Focus:F96-F103
Beard NA, Laver DR, Dulhunty AF (2004) Calsequestrin and the calcium release channel of skeletal and cardiac muscle. Prog Biophys Mol Biol 85(1):33–69
Papp E, Nardai G, Soti C, Csermely, P (2003) Molecular chaperones, stress proteins and redox homeostasis. Biofactors 17(1–4):249–257
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(3):651–66
Nakamura K, Zuppini A, Arnaudeau S, Lynch J, Ahsan I, Krause R, Papp S, Smedt H De, Parys JB, Muller-Esterl W, Lew DP, Krause KH, Demaurex N, Opas M, Michalak M (2001) Functional specialization of calreticulin domains. J Cell Biol 154(5):961–972
Leach MR, Cohen-Doyle MF, Thomas DY, Williams DB (2002) Localization of the lectin, ERp57 binding, and polypeptide binding sites of calnexin and calreticulin. J Biol Chem 277(33):29686–29697
Kapoor M, Ellgaard L, Gopalakrishnapai J, Schirra C, Gemma E, Oscarson S, Helenius A, Surolia A (2004) Mutational analysis provides molecular insight into the carbohydrate-binding region of calreticulin: pivotal roles of tyrosine-109 and aspartate-135 in carbohydrate recognition. Biochemistry 43(1):97–106
Ellgaard L, Riek R, Herrmann T, Guntert P, Braun D, Helenius A, Wuthrich K (2001) NMR structure of the calreticulin P-domain. Proc Natl Acad Sci U S A 98(6):3133–3138
Ellgaard L, Riek R, Braun D, Herrmann T, Helenius A, Wuthrich K (2001) Three-dimensional structure topology of the calreticulin P-domain based on NMR assignment. FEBS Lett 488(1–2):69–73
Vassilakos A, Michalak M, Lehrman MA, Williams DB (1998) Oligosaccharide binding characteristics of the molecular chaperones calnexin and calreticulin. Biochemistry 37(10):3480–3490
Frickel EM, Riek R, Jelesarov I, Helenius A, Wuthrich K, Ellgaard L (2002)TROSY-NMR reveals interaction between ERp57 and the tip of the calreticulin P-domain. Proc Natl Acad Sci U S A 99(4):1954–1959
Baksh S, Michalak M (1991) Expression of calreticulin in Escherichia coli and identification of its Ca2+ binding domains. J Biol Chem 266(32):21458–21465.
Lievremont JP, Rizzuto R, Hendershot L, Meldolesi J (1997) BiP, a major chaperone protein of the endoplasmic reticulum lumen, plays a direct and important role in the storage of the rapidly exchanging pool of Ca2+. J Biol Chem 272(49):30873–30879
Argon Y, Simen BB (1999) GRP94, an ER chaperone with protein and peptide binding properties. Semin Cell Dev Biol 10(5):495–505
Brini M, Carafoli E (2009) Calcium pumps in health and disease. Physiol Rev 89(4):1341–1378
Hovnanian A (2007) SERCA pumps and human diseases. Subcell Biochem 45:337–363
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(5)
Periasamy M, Kalyanasundaram A (2007) SERCA pump isoforms: their role in calcium transport and disease. Muscle Nerve 35(4):430–442
Traaseth NJ, Ha KN, Verardi R, Shi L, Buffy JJ, Masterson LR, Veglia G (2008) Structural and dynamic basis of phospholamban and sarcolipin inhibition of Ca2+-ATPase. Biochemistry 47(1):3–13
Michelangeli F, East JM (2011) A diversity of SERCA Ca2+ pump inhibitors. Biochem Soc Trans 39(3):789–797
Kass GE, Orrenius S (1999) Calcium signaling and cytotoxicity. Environ Health Perspect 107(Suppl 1):25–35
Taylor CW, Dale P (2011) Intracellular Ca2+ channels – A growing community. Mol Cell Endocrinol.
Foskett JK, White C, Cheung KH, Mak DO (2007) Inositol trisphosphate receptor Ca2+ release channels. Physiol Rev 87(2):593–658
Mikoshiba K (2007) IP3 receptor/Ca2+ channel: from discovery to new signaling concepts. J Neurochem 102(5):1426–1446
Mikoshiba K (2007) The IP3 receptor/Ca2+ channel and its cellular function. Biochem Soc Symp (74):9–22
Lanner JT, Georgiou DK, Joshi AD, Hamilton SL (2010) Ryanodine receptors: structure, expression, molecular details, and function. In: Calcium release. Cold Spring Harb Perspect Bio 2(11):a003996
Capes EM, Loaiza R, Valdivia HH (2011) Ryanodine receptors. Skelet Muscle 1(1):18
Verkhratsky A (2002) The endoplasmic reticulum and neuronal calcium signalling. Cell Calcium 32(5–6):393–404
Berridge MJ, Irvine RF (1989) Inositol phosphates and cell signalling. Nature 341(6239):197–205
Taylor CW, Tovey SC (2010) IP3 receptors: toward understanding their activation. Cold Spring Harb Perspect Biol 2(12):a004010
Bezprozvanny I, Watras J (1991) Ehrlich BE Bell-shaped calcium-response curves of Ins(1,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum. Nature 351(6329):751–754
Missiaen L, Smedt, H De, Droogmans G, Casteels R (1992) Ca2+ release induced by inositol 1,4,5-trisphosphate is a steady-state phenomenon controlled by luminal Ca2+ in permeabilized cells. Nature 357(6379):599–602
Missiaen L, Smedt, H De, Droogmans G, Casteels R (1992) Luminal Ca2+ controls the activation of the inositol 1,4,5-trisphosphate receptor by cytosolic Ca2+ . J Biol Chem 267(32):22961–22966
Endo M (2009) Calcium-induced calcium release in skeletal muscle. Physiol Rev 89(4):1153–1176
Lehnart S, Marks AR (2007) Regulation of ryanodine receptors in the heart. Circ Res 101(8):746–749
Marx SO, Gaburjakova J, Gaburjakova M, Henrikson C, Ondrias K, Marks AR (2001) Coupled gating between cardiac calcium release channels (ryanodine receptors). Circ Res 88(11):1151–1158
Mackrill JJ (1999) Protein-protein interactions in intracellular Ca2+ -release channel function. Biochem J 337 (Pt 3): 345–361
Zalk R, Lehnart SE, Marks AR (2007) Modulation of the ryanodine receptor and intracellular calcium. Annu Rev Biochem 76:367–385
Distelhorst CW, Bootman MD (2011) Bcl-2 interaction with the inositol 1,4,5-trisphosphate receptor: Role in Ca2+  signaling and disease. Cell Calcium 50(3):234–241
Decuypere JP, Bultynck G, Parys JB (2011) A dual role for Ca2+ in autophagy regulation. Cell Calcium 50(3):242–250
Rojas-Rivera D, Caballero B, Zamorano S, Lisbona F, Hetz C (2010) Alternative functions of the BCL-2 protein family at the endoplasmic reticulum. Adv Exp Med Biol 687:33–47
Pizzo P, Lissandron V, Capitanio P, Pozzan T (2011) Ca2+ signalling in the Golgi apparatus. Cell Calcium 50(2):184–192
Morgan AJ, Platt FM, Lloyd-Evans E, Galione A (2011) Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease. Biochem J 439(3):349–374
Pinton P, Pozzan T, Rizzuto R (1998) The Golgi apparatus is an inositol 1,4,5-trisphosphate-sensitive Ca2+ store, with functional properties distinct from those of the endoplasmic reticulum. EMBO J. 17(18):5298–5308
Missiaen L, Acker K Van, Baelen K Van, Raeymaekers L, Wuytack F, Parys JB, Smedt H De, Vanoevelen J, Dode L, Rizzuto R, Callewaert G (2004) Calcium release from the Golgi apparatus and the endoplasmic reticulum in HeLa cells stably expressing targeted aequorin to these compartments. Cell Calcium 36(6):479–487
Vanoevelen J, Raeymaekers L, Dode L, Parys JB, Smedt H De, Callewaert G, Wuytack F, Missiaen L (2005) Cytosolic Ca2+ signals depending on the functional state of the Golgi in HeLa cells. Cell Calcium 38(5):489–495
Pizzo P, Lissandron V, Pozzan T (2010) The trans-golgi compartment: A new distinct intracellular Ca store. Commun Integr Biol 3(5):462–464
Lissandron V, Podini P, Pizzo P, Pozzan T (2010) Unique characteristics of Ca2+ homeostasis of the trans-Golgi compartment. Proc Natl Acad Sci U S A 107(20):9198–9203
Zhu MX, Evans AM, Ma J, Parrington J, Galione A (2010) Two-pore channels for integrative Ca signaling. Commun Integr Biol 3(1):12–17
Zhu MX, Ma J, Parrington J, Galione A, Evans AM (2010) TPCs: Endolysosomal channels for Ca2+ mobilization from acidic organelles triggered by NAADP. FEBS Lett 584(10):1966–1974
Galione A (2011) NAADP receptors. Cold Spring Harb Perspect Biol. 3(1):a004036
Galione A, Parrington J, Funnell T (2011) Physiological roles of NAADP-mediated Ca2+ signaling. Sci China Life Sci 54(8):725–732
Calcraft PJ, Ruas M, Pan Z, Cheng X, Arredouani A, Hao X, Tang J, Rietdorf K, Teboul L, Chuang KT, Lin P, **ao R, Wang C, Zhu Y, Lin Y, Wyatt CN, Parrington J, Ma J, Evans AM, Galione A (2009) Zhu MX NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature 459(7246):596–600
Galione A, Morgan AJ, Arredouani A, Davis LC, Rietdorf K, Ruas M, Parrington J (2010) NAADP as an intracellular messenger regulating lysosomal calcium-release channels. Biochem Soc Trans 38(6):1424–1431
Zhu MX, Ma J, Parrington J, Calcraft PJ, Galione A, Evans AM (2010) Calcium signaling via two-pore channels: local or global, that is the question. Am J Physiol Cell Physiol 298(3):C430–441
Galione A, Churchill GC (2002) Interactions between calcium release pathways: multiple messengers and multiple stores. Cell Calcium 32(5–6):343–354
Camello C, Lomax R, Petersen OH, Tepikin AV (2002) Calcium leak from intracellular stores–the enigma of calcium signalling. Cell Calcium 32(5–6):355–361
Coppenolle F Van, Vanden Abeele F, Slomianny C, Flourakis M, Hesketh J, Dewailly E, Prevarskaya N (2004) Ribosome-translocon complex mediates calcium leakage from endoplasmic reticulum stores. J Cell Sci 117(Pt 18):4135–4142
Ong HL, Liu X, Sharma A, Hegde RS, Ambudkar IS (2007) Intracellular Ca2+ release via the ER translocon activates store-operated calcium entry. Pflugers Arch 453(6):797–808
Flourakis M, Coppenolle F Van, Lehen’kyi V, Beck B, Skryma R, Prevarskaya N (2006) Passive calcium leak via translocon is a first step for iPLA2-pathway regulated store operated channels activation. FASEB J 20(8):1215–1217
Amer MS, Li J, O’Regan DJ, Steele DS, Porter KE, Sivaprasadarao A, Beech DJ (2009) Translocon closure to Ca2+ leak in proliferating vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 296(4):H910–916
Denis V, Cyert MS (2002) Internal Ca2+ release in yeast is triggered by hypertonic shock and mediated by a TRP channel homologue. J Cell Biol 156(1):29–34
Berbey C, Weiss N, Legrand C, Allard B (2009) Transient receptor potential canonical type 1 (TRPC1) operates as a sarcoplasmic reticulum calcium leak channel in skeletal muscle. J Biol Chem 284(52):36387–36394
Liu M, Liu MC, Magoulas C, Priestley JV, Willmott NJ (2003) Versatile regulation of cytosolic Ca2+ by vanilloid receptor I in rat dorsal root ganglion neurons. J Biol Chem 278(7):5462–5472
Turner H, Fleig A, Stokes A, Kinet JP, Penner R (2003) Discrimination of intracellular calcium store subcompartments using TRPV1 (transient receptor potential channel, vanilloid subfamily member 1) release channel activity. Biochem J 371(Pt 2):341–50
Gallego-Sandin S, Rodriguez-Garcia A, Alonso MT, Garcia-Sancho J (2009) The endoplasmic reticulum of dorsal root ganglion neurons contains functional TRPV1 channels. J Biol Chem 284(47):32591–3601
Castro J, Aromataris EC, Rychkov GY, Barritt GJ (2009) A small component of the endoplasmic reticulum is required for store-operated Ca2+ channel activation in liver cells: evidence from studies using TRPV1 and taurodeoxycholic acid. Biochem J 418(3):553–566
Bidaux G, Flourakis M, Thebault S, Zholos A, Beck B, Gkika D, Roudbaraki M, Bonnal JL, Mauroy B, Shuba Y, Skryma R, Prevarskaya N (2007) Prostate cell differentiation status determines transient receptor potential melastatin member 8 channel subcellular localization and function. J Clin Invest 117(6):1647–1657
Vassilev PM, Guo L, Chen XZ, Segal Y, Peng JB, Basora N, Babakhanlou H, Cruger G, Kanazirska M, Ye C, Brown EM, Hediger MA, Zhou J (2001) Polycystin-2 is a novel cation channel implicated in defective intracellular Ca2+  homeostasis in polycystic kidney disease. Biochem Biophys Res Commun 282(1):341–350
Koulen P, Cai Y, Geng L, Maeda Y, Nishimura S, Witzgall R, Ehrlich BE, Somlo S (2002) Polycystin-2 is an intracellular calcium release channel. Nat Cell Biol 4(3):191–197
Koulen P, Duncan RS, Liu J, Cohen NE, Yannazzo JA, McClung N, Lockhart CL, Branden M, Buechner M (2005) Polycystin-2 accelerates Ca2+ release from intracellular stores in Caenorhabditis elegans. Cell Calcium 37(6):593–601
Giamarchi A, Padilla F, Crest M, Honore E, Delmas P (2006) TRPP2: Ca2+ -permeable cation channel and more. Cell Mol Biol (Noisy-le-grand) 52(8):105–114
Li Y, Wright JM, Qian F, Germino GG, Guggino WB (2005) Polycystin 2 interacts with type I inositol 1,4,5-trisphosphate receptor to modulate intracellular Ca2+ signaling. J Biol Chem 280(50):41298–41306
Anyatonwu GI, Estrada M, Tian X, Somlo S, Ehrlich BE (2007) Regulation of ryanodine receptor-dependent calcium signaling by polycystin-2. Proc Natl Acad Sci U S A 104(15):6454–6459
Sammels E, Devogelaere B, Mekahli D, Bultynck G, Missiaen L, Parys JB, Cai Y, Somlo S, Smedt H De (2010) Polycystin-2 activation by inositol 1,4,5-trisphosphate-induced Ca2+ release requires its direct association with the inositol 1,4,5-trisphosphate receptor in a signaling microdomain. J Biol Chem 285(24):18794–18805
Wegierski T, Steffl D, Kopp C, Tauber R, Buchholz B, Nitschke R, Kuehn EW, Walz G, Kottgen M (2009) TRPP2 channels regulate apoptosis through the Ca2+ concentration in the endoplasmic reticulum. EMBO J 28(5):490–499
Tu H, Nelson O, Bezprozvanny A, Wang Z, Lee SF, Hao YH, Serneels L, Strooper B De, Yu G, Bezprozvanny I (2006) Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer’s disease-linked mutations. Cell 126(5):981–993
Mattia F de, Gubser C, Dommelen MM van, Visch HJ, Distelmaier F, Postigo A, Luyten T, Parys JB, Smedt H de, Smith GL, Willems PH, Kuppeveld, FJ van (2009) Human Golgi antiapoptotic protein modulates intracellular calcium fluxes. Mol Biol Cell 20(16):3638–3645
Henke N, Lisak DA, Schneider L, Habicht J, Pergande M, Methner A (2011) The ancient cell death suppressor BAX inhibitor-1. Cell Calcium 50(3):251–60
Chae HJ, Kim HR, Xu C, Bailly-Maitre B, Krajewska M, Krajewski S, Banares S, Cui J, Digicaylioglu M, Ke N, Kitada S, Monosov E, Thomas M, Kress CL, Babendure JR, Tsien RY, Lipton SA, Reed JC (2004) BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress. Mol Cell 15(3):355–366
Kim HR, Lee GH, Ha KC, Ahn T, Moon JY, Lee BJ, Cho SG, Kim S, Seo YR, Shin YJ, Chae SW, Reed JC, Chae HJ (2008) Bax Inhibitor-1 Is a pH-dependent regulator of Ca2 + channel activity in the endoplasmic reticulum. J Biol Chem 283(23):15946–15955
Xu C, Xu W, Palmer AE, Reed JC (2008) BI-1 regulates endoplasmic reticulum Ca2+ homeostasis downstream of Bcl-2 family proteins. J Biol Chem 283(17):11477–11484
Ahn T, Yun CH, Chae HZ, Kim HR, Chae HJ (2009) Ca2+/H+ antiporter-like activity of human recombinant Bax inhibitor-1 reconstituted into liposomes. FEBS J 276(8):2285–2291
Bultynck G, Kiviluoto S, Henke N, Luyten T, Rybalchenko V, Ivanova H, Nuyts K, Deborggraeve W, Bezprozvanny I, Parys JB, Smedt H De, Missiaen L, Methner A (2012) The C-terminus of Bax Inhibitor-1 forms a Ca2+ -permeable channel pore. J Biol Chem 287(4):2544–2557
Vanden Abeele F, Bidaux G, Gordienko D, Beck B, Panchin YV, Baranova AV, Ivanov DV, Skryma R, Prevarskaya N (2006) Functional implications of calcium permeability of the channel formed by pannexin 1. J Cell Biol 174(4):535–546
D’Hondt C, Ponsaerts R, Smedt H De, Vinken M, Vuyst E De, Bock M De, Wang N, Rogiers V, Leybaert L, Himpens B, Bultynck G (2011) Pannexin channels in ATP release and beyond: an unexpected rendezvous at the endoplasmic reticulum. Cell Signal 23(2):305–316
Chami M, Gozuacik D, Lagorce D, Brini M, Falson P, Peaucellier G, Pinton P, Lecoeur H, Gougeon ML, Maire M le, Rizzuto R, Brechot C, Paterlini-Brechot P (2001) SERCA1 truncated proteins unable to pump calcium reduce the endoplasmic reticulum calcium concentration and induce apoptosis. J Cell Biol 153(6):1301–1313
Chami M, Oules B, Szabadkai G, Tacine R, Rizzuto R, Paterlini-Brechot P (2008) Role of SERCA1 truncated isoform in the proapoptotic calcium transfer from ER to mitochondria during ER stress. Mol Cell 32(5):641–651
Putney JW Jr (2005) Capacitative calcium entry: sensing the calcium stores. J Cell Biol 169(3):381–382
Putney JW Jr (2007) New molecular players in capacitative Ca2+ entry. J Cell Sci 120(Pt 12):1959–1965
Hogan PG, Lewis RS, Rao A (2010) Molecular basis of calcium signaling in lymphocytes: STIM and ORAI. Annu Rev Immunol 28:491–533
Brandman O, Liou J, Park WS, Meyer T (2007) STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca2+ levels. Cell 131(7):1327–1339
Thomenius MJ, Distelhorst CW (2003) Bcl-2 on the endoplasmic reticulum: protecting the mitochondria from a distance. J Cell Sci 116(Pt 22):4493–4499
Giorgi C, Romagnoli A, Pinton P, Rizzuto R (2008) Ca2+ signaling, mitochondria and cell death. Curr Mol Med 8(2):119–130
Hayashi T, Rizzuto R, Hajnoczky G, Su TP (2009) MAM: more than just a housekeeper. Trends Cell Biol 19(2):81–88
Rizzuto R, Marchi S, Bonora M, Aguiari P, Bononi A, Stefani D De, Giorgi C, Leo S, Rimessi A, Siviero R, Zecchini E, Pinton P (2009) Ca2+ transfer from the ER to mitochondria: when, how and why. Biochim Biophys Acta 1787(11):1342–1351
Contreras L, Drago I, Zampese E, Pozzan T (2010) Mitochondria: the calcium connection. Biochim Biophys Acta 1797(6–7):607–618
Decuypere JP, Monaco G, Missiaen L, Smedt H De, Parys JB, Bultynck G (2011) IP3 Receptors, Mitochondria, and Ca Signaling: Implications for Aging. J Aging Res :920178
Sano R, Annunziata I, Patterson A, Moshiach S, Gomero E, Opferman J, Forte M, d’Azzo A (2009) GM1-ganglioside accumulation at the mitochondria-associated ER membranes links ER stress to Ca2+ -dependent mitochondrial apoptosis. Mol Cell 36(3):500–511
Missiaen L, Parys JB, Sienaert I, Maes K, Kunzelmann K, Takahashi M, Tanzawa K, Smedt H De (1998) Functional properties of the type-3 InsP3 receptor in 16HBE14o- bronchial mucosal cells. J Biol Chem 273(15):8983–8986
Miyakawa T, Maeda A, Yamazawa T, Hirose K, Kurosaki T, Iino M (1999) Encoding of Ca2+ signals by differential expression of IP3 receptor subtypes. EMBO J 18(5):1303–1308
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(49):40892–40900
Chen R, Valencia I, Zhong F, McColl KS, Roderick HL, Bootman MD, Berridge MJ, Conway SJ, Holmes AB, Mignery GA, Velez P, Distelhorst CW (2004) Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate. J Cell Biol 166(2):193–203
Zhong F, Davis MC, McColl KS, Distelhorst CW (2006) Bcl-2 differentially regulates Ca2+ signals according to the strength of T cell receptor activation. J Cell Biol 172(1):127–37
Rong YP, Aromolaran AS, Bultynck G, Zhong F, Li X, McColl K, Matsuyama S, Herlitze S, Roderick HL, Bootman MD, Mignery GA, Parys JB, Smedt H De, Distelhorst CW (2008) Targeting Bcl-2-IP3 receptor interaction to reverse Bcl-2’s inhibition of apoptotic calcium signals. Mol Cell 31(2):255–265
White C, Li C, Yang J, Petrenko NB, Madesh M, Thompson CB, Foskett JK (2005) The endoplasmic reticulum gateway to apoptosis by Bcl-XL modulation of the InsP3R. Nat Cell Biol 7(10):1021–1028
Li C, Wang X, Vais H, Thompson CB, Foskett JK, White C (2007) Apoptosis regulation by Bcl-x(L) modulation of mammalian inositol 1,4,5-trisphosphate receptor channel isoform gating. Proc Natl Acad Sci U S A 104(30):12565–12570
Rong YP, Bultynck G, Aromolaran AS, Zhong F, Parys JB, Smedt H De, Mignery GA, Roderick HL, Bootman MD, Distelhorst CW (2009) The BH4 domain of Bcl-2 inhibits ER calcium release and apoptosis by binding the regulatory and coupling domain of the IP3 receptor. Proc Natl Acad Sci U S A 106(34):14397–14402
Foskett JK, Yang Y, Cheung KH, Vais H (2009) Bcl-xL Regulation of InsP3 Receptor Gating Mediated by Dual Ca2+ Release Channel BH3 Domains. Biophys J 96(3 Suppl 1):391a
Eckenrode EF, Yang J, Velmurugan GV, Foskett JK, White C (2010) Apoptosis protection by Mcl-1 and Bcl-2 modulation of inositol 1,4,5-trisphosphate receptor-dependent Ca2+ signaling. J Biol Chem. 285(18):13678–13684
Oakes SA, Scorrano L, Opferman JT, Bassik MC, Nishino M, Pozzan T, Korsmeyer SJ (2005) Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum. Proc Natl Acad Sci U S A 102(1):105–110
Li C, Fox CJ, Master SR, Bindokas VP, Chodosh LA, Thompson CB (2002) Bcl-XL affects Ca2+  homeostasis by altering expression of inositol 1,4,5-trisphosphate receptors. Proc Natl Acad Sci U S A 99(15):9830–9835
Jones AW, Szabadkai G (2010) Ca2+ transfer from the ER to mitochondria: channeling cell death by a tumor suppressor. Dev Cell 19(6):789–790
Giorgi C, Ito K, Lin HK, Santangelo C, Wieckowski MR, Lebiedzinska M, Bononi A, Bonora M, Duszynski J, Bernardi R, Rizzuto R, Tacchetti C, Pinton P, Pandolfi PP (2010) PML regulates apoptosis at endoplasmic reticulum by modulating calcium release. Science 330(6008):1247–1251
Pinton P, Giorgi C, Pandolfi PP (2011) The role of PML in the control of apoptotic cell fate: a new key player at ER-mitochondria sites. Cell Death Differ 18(9):1450–1456
Boehning D, Patterson RL, Sedaghat L, Glebova NO, Kurosaki T, Snyder SH (2003) Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis. Nat Cell Biol 5(12):1051–1061
Boehning D, Patterson RL, Snyder SH (2004) Apoptosis and calcium: new roles for cytochrome c and inositol 1,4,5-trisphosphate. Cell Cycle 3(3):252–254
Boehning D, Rossum DB van, Patterson RL, Snyder SH (2005) A peptide inhibitor of cytochrome c/inositol 1,4,5-trisphosphate receptor binding blocks intrinsic and extrinsic cell death pathways. Proc Natl Acad Sci U S A 102(5):1466–1471
Monaco G, Decrock E, Akl H, Ponsaerts R, Vervliet T, Luyten T, Maeyer M De, Missiaen L, Distelhorst CW, Smedt H De, Parys JB, Leybaert L, Bultynck G (2011) Selective regulation of IP3-receptor-mediated Ca2+ signaling and apoptosis by the BH4 domain of Bcl-2 versus Bcl-Xl. Cell DeathDiffer 19(2):295–309
Assefa Z, Bultynck G, Szlufcik K, Nadif Kasri N, Vermassen E, Goris J, Missiaen L, Callewaert G, Parys JB, Smedt H De (2004) Caspase-3-induced truncation of type 1 inositol trisphosphate receptor accelerates apoptotic cell death and induces inositol trisphosphate-independent calcium release during apoptosis. J Biol Chem 279(41):43227–43236
Verbert L, Lee B, Kocks SL, Assefa Z, Parys JB, Missiaen L, Callewaert G, Fissore RA, Smedt H De (2008) Bultynck, G., Caspase-3-truncated type 1 inositol 1,4,5-trisphosphate receptor enhances intracellular Ca2+ leak and disturbs Ca2+ signalling. Biol Cell 100(1):39–49
Pearce MM, Wang Y, Kelley GG, Wojcikiewicz RJ (2007) SPFH2 mediates the endoplasmic reticulum-associated degradation of inositol 1,4,5-trisphosphate receptors and other substrates in mammalian cells. J Biol Chem 282(28):20104–20115
Wojcikiewicz RJ, Pearce MM, Sliter DA, Wang Y (2009) When worlds collide: IP3 receptors and the ERAD pathway. Cell Calcium 46(3):147–153
Wang Y, Pearce MM, Sliter DA, Olzmann JA, Christianson JC, Kopito RR, Boeckmann S, Gagen C, Leichner GS, Roitelman J, Wojcikiewicz RJ (2009) SPFH1 and SPFH2 mediate the ubiquitination and degradation of inositol 1,4,5-trisphosphate receptors in muscarinic receptor-expressing HeLa cells. Biochim Biophys Acta 1793(11):1710–1718
Pearce MM, Wormer DB, Wilkens S, Wojcikiewicz RJ (2009) An endoplasmic reticulum (ER) membrane complex composed of SPFH1 and SPFH2 mediates the ER-associated degradation of inositol 1,4,5-trisphosphate receptors. J Biol Chem 284(16):10433–10445
Zhong F, Harr MW, Bultynck G, Monaco G, Parys JB, Smedt H De, Rong YP, Molitoris JK, Lam M, Ryder C, Matsuyama S, Distelhorst, CW (2011) Induction of Ca2+ -driven apoptosis in chronic lymphocytic leukemia cells by peptide-mediated disruption of Bcl-2-IP3 receptor interaction. Blood 117(10):2924–2934
Szado T, Vanderheyden V, Parys JB, Smedt H De, Rietdorf K, Kotelevets L, Chastre E, Khan F, Landegren U, Soderberg O, Bootman MD, Roderick HL (2008) Phosphorylation of inositol 1,4,5-trisphosphate receptors by protein kinase B/Akt inhibits Ca2+ release and apoptosis. Proc Natl Acad Sci U S A 105(7):2427–2432
Xu C, Bailly-Maitre B, Reed JC (2005) Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest 115(10):2656–2664
Rizzuto R, Bastianutto C, Brini M, Murgia M, Pozzan T (1994) Mitochondrial Ca2+ homeostasis in intact cells. J Cell Biol 126(5):1183–1194
Jouaville LS, Pinton P, Bastianutto C, Rutter GA, Rizzuto R (1999) Regulation of mitochondrial ATP synthesis by calcium: evidence for a long-term metabolic priming. Proc Natl Acad Sci U S A 96(24):13807–13812
Campanella M, Pinton P, Rizzuto R (2004) Mitochondrial Ca2+ homeostasis in health and disease. Biol Res 37(4):653–660
Cardenas C, Miller RA, Smith I, Bui T, Molgo J, Muller M, Vais H, Cheung KH, Yang J, Parker I, Thompson CB, Birnbaum MJ, Hallows KR, Foskett JK (2010) Essential regulation of cell bioenergetics by constitutive InsP3 receptor Ca2+ transfer to mitochondria. Cell 142(2):270–283
Joseph SK, Hajnoczky G (2007) IP3 receptors in cell survival and apoptosis: Ca2+  release and beyond. Apoptosis 12(5):951–968
Pinton P, Giorgi C, Siviero R, Zecchini E, Rizzuto R (2008) Calcium and apoptosis: ER-mitochondria Ca2+transfer in the control of apoptosis. Oncogene 27(50):6407–6418
Baumgartner HK, Gerasimenko JV, Thorne C, Ferdek P, Pozzan T, Tepikin AV, Petersen OH, Sutton R, Watson AJ, Gerasimenko OV (2009) Calcium elevation in mitochondria is the main Ca2+ requirement for mitochondrial permeability transition pore (mPTP) opening. J Biol Chem 284(31):20796–20803
Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T, Korsmeyer SJ (2003) BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science. 300 (5616):135–139
Oakes SA, Opferman JT, Pozzan T, Korsmeyer SJ, Scorrano L (2003) Regulation of endoplasmic reticulum Ca2+ dynamics by proapoptotic BCL-2 family members. Biochem Pharmacol 66(8):1335–1340
Oakes SA, Lin SS, Bassik MC (2006) The control of endoplasmic reticulum-initiated apoptosis by the BCL-2 family of proteins. Curr Mol Med 6(1):99–109
Gaut JR, Hendershot LM (1993) The modification and assembly of proteins in the endoplasmic reticulum. Curr Opin Cell Biol 5(4):589–595
Ma Y, Hendershot LM (2004) ER chaperone functions during normal and stress conditions. J Chem Neuroanat 28(1–2):51–65
Yoshida I, Monji A, Tashiro K, Nakamura K, Inoue R, Kanba S (2006) Depletion of intracellular Ca2+ store itself may be a major factor in thapsigargin-induced ER stress and apoptosis in PC12 cells. Neurochem Int 48(8):696–702
Moore CE, Omikorede O, Gomez E, Willars GB, Herbert TP (2011) PERK activation at low glucose concentration is mediated by SERCA pump inhibition and confers preemptive cytoprotection to pancreatic beta-cells. Mol Endocrinol 25(2):315–326
Schroder M, Kaufman RJ (2005) The mammalian unfolded protein response. Annu Rev Biochem 74:739–789
Schroder M, Kaufman RJ (2005) ER stress and the unfolded protein response. Mutat Res 569(1–2):29–63
Malhotra JD, Kaufman RJ (2007) The endoplasmic reticulum and the unfolded protein response. Semin Cell Dev Biol 18(6):716–731
Kim MJ, Byun JY, Yun CH, Park IC, Lee KH, Lee SJ (2008) c-Src-p38 mitogen-activated protein kinase signaling is required for Akt activation in response to ionizing radiation. Mol Cancer Res 6(12):1872–1880
Kimata Y, Kohno K (2011) Endoplasmic reticulum stress-sensing mechanisms in yeast and mammalian cells. Curr Opin Cell Biol 23(2):135–142
Liu H, Bowes RC 3rd, Water B van de, Sillence C, Nagelkerke JF, Stevens JL (1997) Endoplasmic reticulum chaperones GRP78 and calreticulin prevent oxidative stress, Ca2+ disturbances, and cell death in renal epithelial cells. J Biol Chem 272(35):21751–21759
Kudo T, Kanemoto S, Hara H, Morimoto N, Morihara T, Kimura R, Tabira T, Imaizumi K, Takeda M (2008) A molecular chaperone inducer protects neurons from ER stress. Cell Death Differ 15(2):364–375
Wiseman RL, Zhang Y, Lee KP, Harding HP, Haynes CM, Price J, Sicheri F, Ron D (2010) Flavonol activation defines an unanticipated ligand-binding site in the kinase-RNase domain of IRE1. Mol Cell 38(2):291–304
Hayashi T, Su TP (2007) Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca2+ signaling and cell survival. Cell 131(3):596–610
Higo T, Hamada K, Hisatsune C, Nukina N, Hashikawa T, Hattori M, Nakamura T, Mikoshiba K (2010) Mechanism of ER stress-induced brain damage by IP3 receptor. Neuron 68(5):865–878
Timmins JM, Ozcan L, Seimon TA, Li G, Malagelada C, Backs J, Backs T, Bassel-Duby R, Olson EN, Anderson ME, Tabas I (2009) Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways. J Clin Invest 119(10):2925–2941
Ozcan L, Tabas I (2010) Pivotal role of calcium/calmodulin-dependent protein kinase II in ER stress-induced apoptosis. Cell Cycle 9(2):223–224
Dejeans N, Tajeddine N, Beck R, Verrax J, Taper H, Gailly P, Calderon PB (2010) Endoplasmic reticulum calcium release potentiates the ER stress and cell death caused by an oxidative stress in MCF-7 cells. Biochem Pharmacol 79(9):1221–1230
Ruiz A, Matute C, Alberdi E (2009) Endoplasmic reticulum Ca2+  release through ryanodine and IP3 receptors contributes to neuronal excitotoxicity. Cell Calcium 46(4):273–281
Bonilla M, Nastase KK, Cunningham KW (2002) Essential role of calcineurin in response to endoplasmic reticulum stress. EMBO J 21(10):2343–2353
Hoyer-Hansen M, Jaattela M (2007) Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium. Cell Death Differ 14(9):1576–1582
Kouroku Y, Fujita E, Tanida I, Ueno T, Isoai A, Kumagai H, Ogawa S, Kaufman RJ, Kominami E, Momoi T (2007) ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation. Cell Death Differ 14(2):230–239
Hoyer-Hansen M, Bastholm L, Szyniarowski P, Campanella M, Szabadkai G, Farkas T, Bianchi K, Fehrenbacher N, Elling F, Rizzuto R, Mathiasen IS, Jaattela M (2007) Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-beta, and Bcl-2. Mol Cell 25(2):193–205
Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, Asara JM. Fitzpatrick J, Dillin A, Viollet B, Kundu M, Hansen M, Shaw RJ (2011) Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 331(6016):456–461
Mao K, Klionsky DJ (2011) AMPK activates autophagy by phosphorylating ULK1. Circ Res 108(7):787–788
Zhao M, Klionsky DJ (2011) AMPK-dependent phosphorylation of ULK1 induces autophagy. Cell Metab 13(2):119–120
Grotemeier A, Alers S, Pfisterer SG, Paasch F, Daubrawa M, Dieterle A, Viollet B, Wesselborg S, Proikas-Cezanne T, Stork B (2010) AMPK-independent induction of autophagy by cytosolic Ca2+ increase. Cell Signal 22(6):914–925
Momoi T (2006) Conformational diseases and ER stress-mediated cell death: apoptotic cell death and autophagic cell death. Curr Mol Med 6(1):111–118
Torres M, Castillo K, Armisen R, Stutzin A, Soto C, Hetz C (2010) Prion protein misfolding affects calcium homeostasis and sensitizes cells to endoplasmic reticulum stress. PLoS ONE 5(12):e15658
Ding WX, Ni HM, Gao W, Hou YF, Melan MA, Chen X, Stolz DB, Shao ZM, Yin XM (2007) Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival. J Biol Chem 282(7):4702–4710
Li G, Mongillo M, Chin KT, Harding H, Ron D, Marks AR, Tabas I (2009) Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis. J Cell Biol 186(6):783–792
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(1):85–98
Huang G, Yao J, Zeng W, Mizuno Y, Kamm KE, Stull JT, Harding HP, Ron D, Muallem S (2006) ER stress disrupts Ca2+ -signaling complexes and Ca2+ regulation in secretory and muscle cells from PERK-knockout mice. J Cell Sci 119(Pt 1):153–161
Brostrom MA, Prostko CR, Gmitter D, Brostrom CO (1995) Independent signaling of grp78 gene transcription and phosphorylation of eukaryotic initiator factor 2 alpha by the stressed endoplasmic reticulum. J Biol Chem 270(8):4127–4132
Yu Z, Luo H, Fu W, Mattson MP (1999) The endoplasmic reticulum stress-responsive protein GRP78 protects neurons against excitotoxicity and apoptosis: suppression of oxidative stress and stabilization of calcium homeostasis. Exp Neurol 155(2):302–314
Bollo M, Paredes RM, Holstein D, Zheleznova N, Camacho P, Lechleiter JD (2010) Calcineurin interacts with PERK and dephosphorylates calnexin to relieve ER stress in mammals and frogs. PLoS ONE 5(8):e11925
Bastianutto C, Clementi E, Codazzi F, Podini P, Giorgi F De, Rizzuto R, Meldolesi J, Pozzan T (1995) Overexpression of calreticulin increases the Ca2+ capacity of rapidly exchanging Ca2+ stores and reveals aspects of their lumenal microenvironment and function. J Cell Biol 130(4):847–855
John LM, Lechleiter JD, Camacho P (1998) Differential modulation of SERCA2 isoforms by calreticulin. J Cell Biol 142(4):963–973
Roderick HL, Lechleiter JD, Camacho P (2000) Cytosolic phosphorylation of calnexin controls intracellular Ca2+  oscillations via an interaction with SERCA2b. J Cell Biol 149(6):1235–1248
Baksh S, Burns K, Andrin C, Michalak M (1995) Interaction of calreticulin with protein disulfide isomerase. J Biol Chem 270(52):31338–43134
Li Y, Camacho P (2004) Ca2+-dependent redox modulation of SERCA 2b by ERp57. J Cell Biol 164(1):35–46
Premereur N, Branden C Van Den, Roels F (1986) Cytochrome P-450-dependent H2O2 production demonstrated in vivo. Influence of phenobarbital and allylisopropylacetamide. FEBS Lett 199(1):19–22
Davydov DR, Petushkova NA, Bobrovnikova EV, Knyushko TV, Dansette P (2001) Association of cytochromes P450 1A2 and 2B4: are the interactions between different P450 species involved in the control of the monooxygenase activity and coupling? Adv Exp Med Biol 500:335–338
Haynes CM, Titus EA, Cooper AA ( 2004) Degradation of misfolded proteins prevents ER-derived oxidative stress and cell death. Mol Cell 15(5):767–776
Tu BP, Weissman JS (2004) Oxidative protein folding in eukaryotes: mechanisms and consequences. J Cell Biol 164(3):341–346
Hawkins BJ, Irrinki KM, Mallilankaraman K, Lien YC, Wang Y, Bhanumathy CD, Subbiah R, Ritchie MF, Soboloff J, Baba Y, Kurosaki T, Joseph SK, Gill DL, Madesh M (2010) S-glutathionylation activates STIM1 and alters mitochondrial homeostasis. J Cell Biol 190(3):391–405
Ishikawa T, Watanabe N, Nagano M, Kawai-Yamada M, Lam E (2011) Bax inhibitor-1: a highly conserved endoplasmic reticulum-resident cell death suppressor. Cell Death Differ 18(8):1271–1278
Xu Q, Reed JC (1998) Bax inhibitor-1, a mammalian apoptosis suppressor identified by functional screening in yeast. Mol Cell 1(3):337–346
Chae HJ, Ke N, Kim HR, Chen S, Godzik A, Dickman M, Reed JC (2003) Evolutionarily conserved cytoprotection provided by Bax Inhibitor-1 homologs from animals, plants, and yeast. Gene 323:101–113
Lee GH, Kim DS, Kim HT, Lee JW, Chung CH, Ahn T, Lim JM, Kim IK, Chae HJ, Kim HR (2011) Enhanced lysosomal activity is involved in Bax inhibitor-1-induced regulation of the endoplasmic reticulum (ER) stress response and cell death against ER stress: involvement of vacuolar H + -ATPase (V-ATPase). J Biol Chem 286(28):24743–24753
Bailly-Maitre B, Fondevila C, Kaldas F, Droin N, Luciano F, Ricci JE, Croxton R, Krajewska M, Zapata JM, Kupiec-Weglinski JW, Farmer D, Reed JC (2006) Cytoprotective gene bi-1 is required for intrinsic protection from endoplasmic reticulum stress and ischemia-reperfusion injury. Proc Natl Acad Sci U S A 103(8):2809–2814
Westphalen BC, Wessig J, Leypoldt F, Arnold S, Methner A (2005) BI-1 protects cells from oxygen glucose deprivation by reducing the calcium content of the endoplasmic reticulum. Cell Death Differ 12(3):304–3046
Dohm CP, Siedenberg S, Liman J, Esposito A, Wouters FS, Reed JC, Bahr M, Kermer P (2006) Bax inhibitor-1 protects neurons from oxygen-glucose deprivation. J Mol Neurosci 29(1):1–8
Lee GH, Kim HK, Chae SW, Kim DS, Ha KC, Cuddy M, Kress C, Reed JC, Kim HR, Chae HJ (2007) Bax inhibitor-1 regulates endoplasmic reticulum stress-associated reactive oxygen species and heme oxygenase-1 expression. J Biol Chem 282(30):21618–21628
Kim HR, Lee GH, Cho EY, Chae SW, Ahn T, Chae HJ (2009) Bax inhibitor 1 regulates ER-stress-induced ROS accumulation through the regulation of cytochrome P450 2E1. J Cell Sci 122(Pt 8):1126–1133
Lisbona F, Rojas-Rivera D, Thielen, P, Zamorano S, Todd D, Martinon F, Glavic A, Kress C, Lin JH, Walter P, Reed JC, Glimcher LH, Hetz C (2009) BAX inhibitor-1 is a negative regulator of the ER stress sensor IRE1alpha. Mol Cell 33(6):679–691
Hetz C, Bernasconi P, Fisher J, Lee AH, Bassik MC, Antonsson B, Brandt GS, Iwakoshi NN, Schinzel A, Glimcher LH, Korsmeyer SJ ( 2006) Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha. Science 312(5773):572–576
Rutkowski DT, Arnold SM, Miller CN, Wu J, Li J, Gunnison KM, Mori K, Sadighi Akha AA, Raden D, Kaufman RJ (2006) Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins. PLoS Biol 4(11):e374
Castillo K, Rojas-Rivera D, Lisbona F, Caballero B, Nassif M, Court FA, Schuck S, Ibar C, Walter P, Sierralta J, Glavic A, Hetz C (2011) BAX inhibitor-1 regulates autophagy by controlling the IRE1alpha branch of the unfolded protein response. EMBO J 30(21):4465–4478
Acknowledgments
The authors wish to thank the Research Council of the K.U. Leuven and the Research Foundation – Flanders (F.W.O.) for their support of the research work performed in their lab. We also wish to apologize to those whose research papers in this field were not included in this book chapter. We also wish to thank our national and international collaborators in this field for fruitful discussions.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Vervliet, T., Kiviluoto, S., Bultynck, G. (2012). ER Stress and UPR Through Dysregulated ER Ca2+ Homeostasis and Signaling. In: Agostinis, P., Afshin, S. (eds) Endoplasmic Reticulum Stress in Health and Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4351-9_5
Download citation
DOI: https://doi.org/10.1007/978-94-007-4351-9_5
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-4350-2
Online ISBN: 978-94-007-4351-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)