Abstract
Since its introduction in 1930 by physiologist Walter Bradford Cannon, the concept of homeostasis remains the cardinal tenet of biologic regulation. Cells have evolved a highly integrated network of control mechanisms, including positive and negative feedback loops, to safeguard homeostasis in face of a wide range of stimuli. Such control mechanisms ultimately orchestrate cell death, division and repair in a manner concordant with cellular energy and ionic balance to achieve proper biologic fitness. The interdependence of these homeostatic pathways is also evidenced by shared control points that decode intra- and extracellular cues into defined effector responses.
As critical control points of the intrinsic apoptotic pathway, the BCL-2 family of cell death regulators plays an important role in cellular homeostasis.1–3 The different anti- and pro-apoptotic members of this family form a highly selective network of functional interactions that ultimately governs the permeabilization of the mitochondrial outer membrane and subsequent release of apoptogenic factors such as cytochrome c.4 The advent of loss- and gain-of-function genetic models for the various BCL-2 family proteins has not only provided important insights into apoptosis mechanisms but also uncovered unanticipated roles for these proteins in other physiologic pathways beyond apoptosis (Fig. 1). Here, we turn our attention to these alternative cellular functions for BCL-2 proteins. We begin with a brief introduction of the cast of characters originally known for their capacity to regulate apoptosis and continue to highlight recent advances that have shaped and reshaped our views on their physiologic relevance in integration of apoptosis with other homeostatic pathways.
Physiologic pathways regulated by BCL-2 family proteins.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Chipuk JE, Green DR. How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol 2008; 18(4):157–164.
Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell 2004; 116(2):205–219.
Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 2008; 9(1):47–59.
Leber B, Lin J, Andrews DW. Embedded together: the life and death consequences of interaction of the BCL-2 family with membranes. Apoptosis 2007; 12(5):897–911.
Lindsten T, Ross AJ, King A et al. The combined functions of proapoptotic BCL-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell 2000; 6(6):1389–1399.
Wei MC, Zong WX, Cheng EH et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 2001; 292(5517):727–730.
Cheng WC, Berman SB, Ivanovska I et al. Mitochondrial factors with dual roles in death and survival. Oncogene 2006; 25(34):4697–4705.
Colombini M. VDAC: the channel at the interface between mitochondria and the cytosol. Mol Cell Biochem 2004; 256–257(1–2):107–115.
Rostovtseva TK, Tan W, Colombini M. On the role of VDAC in apoptosis: fact and fiction. J Bioenerg Biomembr 2005; 37(3):129–142.
Baines CP, Kaiser RA, Sheiko T et al. Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol 2007; 9(5):550–555.
Malia TJ, Wagner G. NMR structural investigation of the mitochondrial outer membrane protein VDAC and its interaction with antiapoptotic Bcl-xL. Biochemistry 2007; 46(2):514–525.
Shimizu S, Narita M, Tsujimoto Y. BCL-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature 1999; 399(6735):483–487.
Vander Heiden MG, Li XX, Gottleib E et al. Bcl-xL promotes the open configuration of the voltage-dependent anion channel and metabolite passage through the outer mitochondrial membrane. J Biol Chem 2001; 276(22):19414–19419.
Lee AC, Zizi M, Colombini M. Beta-NADH decreases the permeability of the mitochondrial outer membrane to ADP by a factor of 6. J Biol Chem 1994; 269(49):30974–30980.
Hiller S, Garces RG, Malia TJ et al. Solution structure of the integral human membrane protein VDAC-1 in detergent micelles. Science 2008; 321(5893):1206–1210.
Schwarzer C, Barnikol-Watanabe S, Thinnes FP et al. Voltage-dependent anion-selective channel (VDAC) interacts with the dynein light chain Tctex1 and the heat-shock protein PBP74. Int J Biochem Cell Biol 2002; 34(9):1059–1070.
Carre M, Andre N, Carles G et al. Tubulin is an inherent component of mitochondrial membranes that interacts with the voltage-dependent anion channel. J Biol Chem 2002; 277(37):33664–33669.
Rostovtseva TK, Sheldon KL, Hassanzadeh E et al. Tubulin binding blocks mitochondrial voltage-dependent anion channel and regulates respiration. Proc Natl Acad Sci USA 2008; 105(48):18746–18751.
Xu X, Forbes JG, Colombini M. Actin modulates the gating of Neurospora crassa VDAC. J Membr Biol 2001; 180(1):73–81.
Pastorino JG, Hoek JB. Regulation of hexokinase binding to VDAC. J Bioenerg Biomembr 2008; 40(3):171–182.
Rostovtseva TK, Kazemi N, Weinrich M et al. Voltage gating of VDAC is regulated by nonlamellar lipids of mitochondrial membranes. J Biol Chem 2006; 281(49):37496–37506.
Baines CP, Song CX, Zheng YT et al. Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria. Circ Res 2003; 92(8):873–880.
Bera AK, Ghosh S. Dual mode of gating of voltage-dependent anion channel as revealed by phosphorylation. J Struct Biol 2001; 135(1):67–72.
Pastorino JG, Hoek JB, Shulga N. Activation of glycogen synthase kinase 3beta disrupts the binding of hexokinase II to mitochondria by phosphorylating voltage-dependent anion channel and potentiates chemotherapy-induced cytotoxicity. Cancer Res 2005; 65(22):10545–10554.
Le Mellay V, Troppmair J, Benz R et al. Negative regulation of mitochondrial VDAC channels by C-Raf kinase. BMC Cell Biol 2002; 3:14.
Roy SS, Madesh M, Davies E et al. Bad targets the permeability transition pore independent of Bax or Bak to switch between Ca2+-dependent cell survival and death. Mol Cell 2009; 33(3):377–388.
Mattson MP, Gleichmann M, Cheng A. Mitochondria in neuroplasticity and neurological disorders. Neuron 2008; 60(5):748–766.
Jonas EA, Buchanan J, Kaczmarek LK. Prolonged activation of mitochondrial conductances during synaptic transmission. Science 1999; 286(5443):1347–1350.
Jonas EA, Hoit D, Hickman JA et al. Modulation of synaptic transmission by the BCL-2 family protein BCL-xL. J Neurosci 2003; 23(23):8423–8431.
Hickman JA, Hardwick JM, Kaczmarek LK et al. Bcl-xL inhibitor ABT-737 reveals a dual role for Bcl-xL in synaptic transmission. J Neurophysiol 2008; 99(3):1515–1522.
Duchen MR. Mitochondria and calcium: from cell signalling to cell death. J Physiol 2000; 529 Pt 1:57–68.
Graier WF, Frieden M, Malli R. Mitochondria and Ca(2+) signaling: old guests, new functions. Pflugers Arch 2007; 455(3):375–396.
Csordas G, Thomas AP, Hajnoczky G. Quasi-synaptic calcium signal transmission between endoplasmic reticulum and mitochondria. EMBO J 1999; 18(1):96–108.
Rizzuto R, Brini M, Murgia M et al. Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria. Science 1993; 262(5134):744–747.
Rizzuto R, Pinton P, Carrington W et al. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 1998; 280(5370):1763–1766.
Csordas G, Renken C, Varnai P et al. Structural and functional features and significance of the physical linkage between ER and mitochondria. J Cell Biol 2006; 174(7):915–921.
de Brito OM, Scorrano L. Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 2008; 456(7222):605–610.
Simmen T, Aslan JE, Blagoveshchenskaya AD et al. PACS-2 controls endoplasmic reticulum-mitochondria communication and Bid-mediated apoptosis. EMBO J 2005; 24(4):717–729.
Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 2003; 4(7):517–529.
Orrenius S, Zhivotovsky B, Nicotera P. Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 2003; 4(7):552–565.
Rong Y, Distelhorst CW. BCL-2 protein family members: versatile regulators of calcium signaling in cell survival and apoptosis. Annu Rev Physiol 2008; 70:73–91.
Germain M, Mathai JP, McBride HM et al. Endoplasmic reticulum BIK initiates DRP1-regulated remodelling of mitochondrial cristae during apoptosis. EMBO 2005; 24(8):1546–1556.
Mathai JP, Germain M, Shore GC. BH3-only BIK regulates BAX, BAK-dependent release of Ca2+ from endoplasmic reticulum stores and mitochondrial apoptosis during stress-induced cell death. J Biol Chem 2005; 280(25):23829–23836.
Morishima N, Nakanishi K, Tsuchiya K et al. Translocation of Bim to the endoplasmic reticulum (ER) mediates ER stress signaling for activation of caspase-12 during ER stress-induced apoptosis. J Biol Chem 2004; 279(48):50375–50381.
Scorrano L, Oakes SA, Opferman JT et al. BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science 2003; 300(5616):135–139.
Zong WX, Li C, Hatzivassiliou G et al. Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. J Cell Biol 2003; 162(1):59–69.
Baffy G, Miyashita T, Williamson JR et al. Apoptosis induced by withdrawal of interleukin-3 (IL-3) from an IL-3-dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced BCL-2 oncoprotein production. J Biol Chem 1993; 268(9):6511–6519.
Carvalho AC, Sharpe J, Rosenstock TR et al. Bax affects intracellular Ca2+ stores and induces Ca2+ wave propagation. Cell Death Differ 2004; 11(12):1265–1276.
Csordas G, Madesh M, Antonsson B et al. tcBid promotes Ca(2+) signal propagation to the mitochondria: control of Ca(2+) permeation through the outer mitochondrial membrane. EMBO J 2002; 21(9):2198–2206.
Lam M, Dubyak G, Chen L et al. Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes. Proc Natl Acad Sci USA 1994; 91(14):6569–6573.
Nutt LK, Pataer A, Pahler J et al. Bax and Bak promote apoptosis by modulating endoplasmic reticular and mitochondrial Ca2+ stores. J Biol Chem 2002; 277(11):9219–9225.
Pinton P, Ferrari D, Rapizzi E et al. The Ca2+ concentration of the endoplasmic reticulum is a key determinant of ceramide-induced apoptosis: significance for the molecular mechanism of BCL-2 action. EMBO J 2001; 20(11):2690–2701.
Wang NS, Unkila MT, Reineks EZ et al. Transient expression of wild-type or mitochondrially targeted BCL-2 induces apoptosis, whereas transient expression of endoplasmic reticulum-targeted BCL-2 is protective against Bax-induced cell death. J Biol Chem 2001; 276(47):44117–44128.
White C, Li C, Yang J et al. The endoplasmic reticulum gateway to apoptosis by Bcl-X(L) modulation of the InsP3R. Nat Cell Biol 2005; 7(10):1021–1028.
Heath-Engel HM, Chang NC, Shore GC. The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family. Oncogene 2008; 27(50):6419–6433.
Pinton P, Giorgi C, Siviero R et al. Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis. Oncogene 2008; 27(50):6407–6418.
Chami M, Prandini A, Campanella M et al. BCL-2 and Bax exert opposing effects on Ca2+ signaling, which do not depend on their putative pore-forming region. J Biol Chem 2004; 279(52):54581–54589.
Chen R, Valencia I, Zhong F et al. 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 2004; 166(2):193–203.
Oakes SA, Scorrano L, Opferman JT et al. Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum. Proc Natl Acad Sci USA 2005; 102(1):105–110.
Dremina ES, Sharov VS, Kumar K et al. Anti-apoptotic protein BCL-2 interacts with and destabilizes the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA). Biochem J 2004; 383(Pt 2):361–370.
Dremina ES, Sharov VS, Schoneich C. Displacement of SERCA from SR lipid caveolae-related domains by BCL-2: a possible mechanism for SERCA inactivation. Biochemistry 2006; 45(1):175–184.
Kuo TH, Kim HR, Zhu L et al. Modulation of endoplasmic reticulum calcium pump by BCL-2. Oncogene 1998; 17(15):1903–1910.
Distelhorst CW, Shore GC. BCL-2 and calcium: controversy beneath the surface. Oncogene 2004; 23(16):2875–2880.
Palmer AE, Jin C, Reed JC et al. BCL-2-mediated alterations in endoplasmic reticulum Ca2+ analyzed with an improved genetically encoded fluorescent sensor. Proc Natl Acad Sci USA 2004; 101(50):17404–17409.
Pinton P, Ferrari D, Magalhaes P et al. Reduced loading of intracellular Ca(2+) stores and downregulation of capacitative Ca(2+) influx in BCL-2-overexpressing cells. J Cell Biol 2000; 148(5):857–862.
Erin N, Bronson SK, Billingsley ML. Calcium-dependent interaction of calcineurin with BCL-2 in neuronal tissue. Neuroscience 2003; 117(3):541–555.bl]
Yamamoto K, Ichijo H, Korsmeyer SJ. BCL-2 Is Phosphorylated and Inactivated by an ASK1/ Jun N-Terminal Protein Kinase Pathway Normally Activated at G(2)/M. Mol Cell Biol 1999; 19(12):8469–8478.
Bassik MC, Scorrano L, Oakes SA et al. Phosphorylation of BCL-2 regulates ER Ca2+ homeostasis and apoptosis. EMBO J 2004; 23(5):1207–1216.
Booth C, Koch GL. Perturbation of cellular calcium induces secretion of luminal ER proteins. Cell 1989; 59(4):729–737.
Zhong F, Davis MC, McColl KS et al. BCL-2 differentially regulates Ca2+ signals according to the strength of T-cell receptor activation. J Cell Biol 2006; 172(1):127–137.
Hajnoczky G, Robb-Gaspers LD, Seitz MB et al. Decoding of cytosolic calcium oscillations in the mitochondria. Cell 1995; 82(3):415–424.
Lasorsa FM, Pinton P, Palmieri L et al. Recombinant expression of the Ca(2+)-sensitive aspartate/ glutamate carrier increases mitochondrial ATP production in agonist-stimulated Chinese hamster ovary cells. J Biol Chem 2003; 278(40):38686–38692.
Denton RM, McCormack JG, Edgell NJ. Role of calcium ions in the regulation of intramitochondrial metabolism. Effects of Na+, Mg2+ and ruthenium red on the Ca2+-stimulated oxidation of oxoglutarate and on pyruvate dehydrogenase activity in intact rat heart mitochondria. Biochem J 1980; 190(1):107–117.
Robb-Gaspers LD, Burnett P, Rutter GA et al. Integrating cytosolic calcium signals into mitochondrial metabolic responses. EMBO 1998; 17(17):4987–5000.
Territo PR, Mootha VK, French SA et al. Ca(2+) activation of heart mitochondrial oxidative phosphorylation: role of the F(0)/F(1)-ATPase. Am J Physiol Cell Physiol 2000; 278(2):C423–435.
Jouaville LS, Pinton P, Bastianutto C et al. Regulation of mitochondrial ATP synthesis by calcium: evidence for a long-term metabolic priming. Proc Natl Acad Sci USA 1999; 96(24):13807–13812.
Szalai G, Krishnamurthy R, Hajnoczky G. Apoptosis driven by IP(3)-linked mitochondrial calcium signals. EMBO J 1999; 18(22):6349–6361.
Pacher P, Hajnoczky G. Propagation of the apoptotic signal by mitochondrial waves. EMBO J 2001; 20(15):4107–4121.
Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 2000; 1(1):11–21.
Frey TG, Mannella CA. The internal structure of mitochondria. Trends Biochem Sci 2000; 25(7):319–324.
Mannella CA. Structure and dynamics of the mitochondrial inner membrane cristae. Biochim Biophys Acta 2006; 1763(5–6):542–548.
Hackenbrock CR. Ultrastructural bases for metabolically linked mechanical activity in mitochondria. I. Reversible ultrastructural changes with change in metabolic steady state in isolated liver mitochondria. J Cell Biol 1966; 30(2):269–297.
Chen H, Chan DC. Mitochondrial dynamics in mammals. Curr Top Dev Biol 2004; 59:119–144.
Shaw JM, Nunnari J. Mitochondrial dynamics and division in budding yeast. Trends Cell Biol 2002; 12(4):178–184.
Twig G, Elorza A, Molina AJ et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO 2008; 27(2):433–446.
Bleazard W, McCaffery JM, King EJ et al. The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nat Cell Biol 1999; 1(5):298–304.
James DI, Parone PA, Mattenberger Y et al. hFis1, a novel component of the mammalian mitochondrial fission machinery. J Biol Chem 2003; 278(38):36373–36379.
Labrousse AM, Zappaterra MD, Rube DA et al. C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane. Mol Cell 1999; 4(5):815–826.
Mozdy AD, McCaffery JM, Shaw JM. Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. J Cell Biol 2000; 151(2):367–380.
Smirnova E, Griparic L, Shurland DL et al. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol Biol Cell 2001; 12(8):2245–2256.
Stojanovski D, Koutsopoulos OS, Okamoto K et al. Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology. J Cell Sci 2004; 117(Pt 7):1201–1210.
Yoon Y, Krueger EW, Oswald BJ et al. The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Mol Cell Biol 2003; 23(15):5409–5420.
Cipolat S, Rudka T, Hartmann D et al. Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling. Cell 2006; 126(1):163–175.
Frezza C, Cipolat S, Martins de Brito O et al. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell 2006; 126(1):177–189.
Hermann GJ, Thatcher JW, Mills JP et al. Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p. J Cell Biol 1998; 143(2):359–373.
Koshiba T, Detmer SA, Kaiser JT et al. Structural basis of mitochondrial tethering by mitofusin complexes. Science 2004; 305(5685):858–862.
Rapaport D, Brunner M, Neupert W et al. Fzo1p is a mitochondrial outer membrane protein essential for the biogenesis of functional mitochondria in Saccharomyces cerevisiae. J Biol Chem 1998; 273(32):20150–20155.
Wong ED, Wagner JA, Gorsich SW et al. The dynamin-related GTPase, Mgm1p, is an intermembrane space protein required for maintenance of fusion competent mitochondria. J Cell Biol 2000; 151(2):341–352.
Desagher S, Martinou JC. Mitochondria as the central control point of apoptosis. Trends Cell Biol 2000; 10(9):369–377.
Frank S, Gaume B, Bergmann-Leitner ES et al. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev Cell 2001; 1(4):515–525.
Karbowski M, Lee YJ, Gaume B et al. Spatial and temporal association of Bax with mitochondrial fission sites, Drp1 and Mfn2 during apoptosis. J Cell Biol 2002; 159(6):931–938.
Cassidy-Stone A, Chipuk JE, Ingerman E et al. Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell 2008; 14(2):193–204.
Goyal G, Fell B, Sarin A et al. Role of mitochondrial remodeling in programmed cell death in Drosophila melanogaster. Dev Cell 2007; 12(5):807–816.
Lee YJ, Jeong SY, Karbowski M et al. Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1 and Opa1 in apoptosis. Mol Biol Cell 2004; 15(11):5001–5011.
Parone PA, James DI, Da Cruz S et al. Inhibiting the mitochondrial fission machinery does not prevent Bax/Bak-dependent apoptosis. Mol Cell Biol 2006; 26(20):7397–7408.
Neuspiel M, Zunino R, Gangaraju S et al. Activated mitofusin 2 signals mitochondrial fusion, interferes with Bax activation and reduces susceptibility to radical induced depolarization. J Biol Chem 2005; 280(26):25060–25070.
Wasiak S, Zunino R, McBride HM. Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death. J Cell Biol 2007; 177(3):439–450.
Niemann A, Ruegg M, La Padula V et al. Ganglioside-induced differentiation associated protein 1 is a regulator of the mitochondrial network: new implications for Charcot-Marie-Tooth disease. J Cell Biol 2005; 170(7):1067–1078.
Szabadkai G, Simoni AM, Chami M et al. Drp-1-dependent division of the mitochondrial network blocks intraorganellar Ca2+ waves and protects against Ca2+-mediated apoptosis. Mol Cell 2004; 16(1):59–68.
Tondera D, Czauderna F, Paulick K et al. The mitochondrial protein MTP18 contributes to mitochondrial fission in mammalian cells. J Cell Sci 2005; 118(Pt 14):3049–3059.
Tondera D, Santel A, Schwarzer R et al. Knockdown of MTP18, a novel phosphatidylinositol 3-kinase-dependent protein, affects mitochondrial morphology and induces apoptosis. J Biol Chem 2004; 279(30):31544–31555.
Taguchi N, Ishihara N, Jofuku A et al. Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission. J Biol Chem 2007; 282(15):11521–11529.
Szabadkai G, Simoni AM, Bianchi K et al. Mitochondrial dynamics and Ca2+ signaling. Biochim Biophys Acta 2006; 1763(5–6):442–449.
Brooks C, Wei Q, Feng L et al. Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins. Proc Natl Acad Sci USA 2007; 104(28):11649–11654.
Karbowski M, Norris KL, Cleland MM et al. Role of Bax and Bak in mitochondrial morphogenesis. Nature 2006; 443(7112):658–662.
Delivani P, Adrain C, Taylor RC et al. Role for CED-9 and Egl-1 as regulators of mitochondrial fission and fusion dynamics. Mol Cell 2006; 21(6):761–773.
Li H, Chen Y, Jones AF et al. Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons. Proc Natl Acad Sci USA 2008; 105(6):2169–2174.
Li Z, Okamoto K, Hayashi Y et al. The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 2004; 119(6):873–887.
Verstreken P, Ly CV, Venken KJ et al. Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions. Neuron 2005; 47(3):365–378.
Berman SB, Chen YB, Qi B et al. Bcl-x L increases mitochondrial fission, fusion and biomass in neurons. J Cell Biol 2009; 184(5):707–719.
Breckenridge DG, Kang BH, Xue D. BCL-2 Proteins EGL-1 and CED-9 Do Not Regulate Mitochondrial Fission or Fusion in Caenorhabditis elegans. Curr Biol 2009.
Jagasia R, Grote P, Westermann B et al. DRP-1-mediated mitochondrial fragmentation during EGL-1-induced cell death in C. elegans. Nature 2005; 433(7027):754–760.
Danial NN, Gramm CF, Scorrano L et al. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 2003; 424(6951):952–956.
Matschinsky FM, Magnuson MA, Zelent D et al. The network of glucokinase-expressing cells in glucose homeostasis and the potential of glucokinase activators for diabetes therapy. Diabetes 2006; 55(1):1–12.
Danial NN, Walensky LD, Zhang CY et al. Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nat Med 2008; 14(2):144–153.
Arden C, Baltrusch S, Agius L. Glucokinase regulatory protein is associated with mitochondria in hepatocytes. FEBS Lett 2006; 580(8):2065–2070.
Wilson JE. Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J Exp Biol 2003; 206(Pt 12):2049–2057.
Wiederkehr A, Wollheim CB. Minireview: implication of mitochondria in insulin secretion and action. Endocrinology 2006; 147(6):2643–2649.
Balasubramanian R, Karve A, Kandasamy M et al. A role for F-actin in hexokinase-mediated glucose signaling. Plant Physiol 2007; 145(4):1423–1434.
Giege P, Heazlewood JL, Roessner-Tunali U et al. Enzymes of glycolysis are functionally associated with the mitochondrion in Arabidopsis cells. Plant Cell 2003; 15(9):2140–2151.
Murata T, Katagiri H, Ishihara H et al. Colocalization of glucokinase with actin filaments. FEBS Lett 1997; 406(1–2):109–113.
Waingeh VF, Gustafson CD, Kozliak EI et al. Glycolytic enzyme interactions with yeast and skeletal muscle F-actin. Biophys J 2006; 90(4):1371–1384.
Zhou YP, Pena JC, Roe MW et al. Overexpression of Bcl-x(L) in beta-cells prevents cell death but impairs mitochondrial signal for insulin secretion. Am J Physiol Endocrinol Metab 2000; 278(2):E340–351.
Walensky LD, Pitter K, Morash J et al. A stapled BID BH3 helix directly binds and activates BAX. Mol Cell 2006; 24(2):199–210.
Bose AK, Mocanu MM, Carr RD et al. Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. Diabetes 2005; 54(1):146–151.
Liu W, Chin-Chance C, Lee EJ et al. Activation of phosphatidylinositol 3-kinase contributes to insulin-like growth factor I-mediated inhibition of pancreatic beta-cell death. Endocrinology 2002; 143(10):3802–3812.
Danial NN. BAD: undertaker by night, candyman by day Oncogene. 2009; in press.
Harada H, Andersen JS, Mann M et al. p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD. Proc Natl Acad Sci USA 2001; 98(17):9666–9670.
Tan Y, Demeter MR, Ruan H et al. BAD Ser-155 phosphorylation regulates BAD/BCL-XL interaction and cell survival. J Biol Chem 2000; 275(33):25865–25869.
Yu C, Minemoto Y, Zhang J et al. JNK suppresses apoptosis via phosphorylation of the proapoptotic BCL-2 family protein BAD. Mol Cell 2004; 13(3):329–340.
Deng H, Yu F, Chen J et al. Phosphorylation of Bad at Thr-201 by JNK1 promotes glycolysis through activation of phosphofructokinase-1. J Biol Chem 2008; 283(30):20754–20760.
Smith WE, Langer S, Wu C et al. Molecular coordination of hepatic glucose metabolism by the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase:glucokinase complex. Mol Endocrinol 2007; 21(6):1478–1487.
Karantza-Wadsworth V, Patel S, Kravchuk O et al. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev 2007; 21(13):1621–1635.
Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008; 132(1):27–42.
Fimia GM, Stoykova A, Romagnoli A et al. Ambral regulates autophagy and development of the nervous system. Nature 2007; 447(7148):1121–1125.
Liang C, Feng P, Ku B et al. Autophagic and tumour suppressor activity of a novel Beclin l-binding protein UVRAG. Nat Cell Biol 2006; 8(7):688–699.
Takahashi Y, Coppola D, Matsushita N et al. Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat Cell Biol 2007; 9(10):1142–1151.
Levine B, Klionsky DJ. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 2004; 6(4):463–477.
Geng J, Klionsky DJ. The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. ‘Protein modifications: beyond the usual suspects’ review series. EMBO Rep 2008; 9(9):859–864.
Lum JJ, DeBerardinis RJ, Thompson CB. Autophagy in metazoans: cell survival in the land of plenty. Nat Rev Mol Cell Biol 2005; 6(6):439–448.
Sarbassov DD, Ali SM, Sabatini DM. Growing roles for the mTOR pathway. Curr Opin Cell Biol 2005; 17(6):596–603.
Diaz-Troya S, Perez-Perez ME, Florencio FJ et al. The role of TOR in autophagy regulation from yeast to plants and mammals. Autophagy 2008; 4(7):851–865.
Lum JJ, Bauer DE, Kong M et al. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 2005; 120(2):237–248.
Levine B, Yuan J. Autophag y in cell death: an innocent convict? J Clin Invest 2005; 115(10):2679–2688.
Lockshin RA, Zakeri Z. Apoptosis, autophag y and more. Int J Biochem Cell Biol 2004; 36(12):2405–2419.
Kroemer G, Levine B. Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol 2008; 9(12):1004–1010.
Liang XH, Kleeman LK, Jiang HH et al. Protection against fatal Sindbis virus encephalitis by beclin, a novel BCL-2-interacting protein. J Virol 1998; 72(11):8586–8596.
Pattingre S, Tassa A, Qu X et al. BCL-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 2005; 122(6):927–939.
Maiuri MC, Le Toumelin G, Criollo A et al. Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J 2007; 26(10):2527–2539.
Oberstein A, Jeffrey PD, Shi Y. Crystal structure of the BCL-XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3-only protein. J Biol Chem 2007; 282(17):13123–13132.
Erlich S, Mizrachy L, Segev O et al. Differential interactions between Beclin 1 and BCL-2 family members. Autophagy 2007; 3(6):561–568.
Liang XH, Jackson S, Seaman M et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999; 402(6762):672–676.
Wei Y, Pattingre S, Sinha S et al. JNK1-mediated phosphorylation of BCL-2 regulates starvation-induced autophagy. Mol Cell 2008; 30(6):678–688.
Abedin MJ, Wang D, McDonnell MA et al. Autophagy delays apoptotic death in breast cancer cells following DNA damage. Cell Death Differ 2007; 14(3):500–510.
Daido S, Kanzawa T, Yamamoto A et al. Pivotal role of the cell death factor BNIP3 in ceramide-induced autophagic cell death in malignant glioma cells. Cancer Res 2004; 64(12):4286–4293.
Hamacher-Brady A, Brady NR, Logue SE et al. Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. Cell Death Differ 2007; 14(1):146–157.
Rashmi R, Pillai SG, Vijayalingam S et al. BH3-only protein BIK induces caspase-independent cell death with autophagic features in BCL-2 null cells. Oncogene 2008; 27(10):1366–1375.
Tracy K, Dibling BC, Spike BT et al. BNIP3 is an RB/E2F target gene required for hypoxia-induced autophagy. Mol Cell Biol 2007; 27(17):6229–6242.
Zhang J, Ney PA. NIX induces mitochondrial autophagy in reticulocytes. Autophagy 2008; 4(3):354–356.
Oltersdorf T, Elmore SW, Shoemaker AR et al. An inhibitor of BCL-2 family proteins induces regression of solid tumours. Nature 2005; 435(7042):677–681.
Germain M, Mathai JP, Shore GC. BH-3-only BIK functions at the endoplasmic reticulum to stimulate cytochrome c release from mitochondria. J Biol Chem 2002; 277(20):18053–18060.
Criollo A, Maiuri MC, Tasdemir E et al. Regulation of autophagy by the inositol trisphosphate receptor. Cell Death Differ 2007; 14(5):1029–1039.
Hoyer-Hansen M, Bastholm L, Szyniarowski P et al. Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-beta and BCL-2. Mol Cell 2007; 25(2):193–205.
Schweers RL, Zhang J, Randall MS et al. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci USA 2007; 104(49):19500–19505.
Sandoval H, Thiagarajan P, Dasgupta SK et al. Essential role for Nix in autophagic maturation of erythroid cells. Nature 2008; 454(7201):232–235.
Heynen MJ, Tricot G, Verwilghen RL. Autophagy of mitochondria in rat bone marrow erythroid cells. Relation to nuclear extrusion. Cell Tissue Res 1985; 239(1):235–239.
Koury MJ, Koury ST, Kopsombut P et al. In vitro maturation of nascent reticulocytes to erythrocytes. Blood 2005; 105(5):2168–2174.
Waugh RE, McKenney JB, Bauserman RG et al. Surface area and volume changes during maturation of reticulocytes in the circulation of the baboon. J Lab Clin Med 1997; 129(5):527–535.
Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 2007; 8(7):519–529.
Scheuner D, Kaufman RJ. The unfolded protein response: a pathway that links insulin demand with beta-cell failure and diabetes. Endocr Rev 2008; 29(3):317–333.
Todd DJ, Lee AH, Glimcher LH. The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev Immunol 2008; 8(9):663–674.
Fujita E, Kouroku Y, Isoai A et al. Two endoplasmic reticulum-associated degradation (ERAD) systems for the novel variant of the mutant dysferlin: ubiquitin/proteasome ERAD(I) and autophagy/lysosome ERAD(II). Hum Mol Genet 2007; 16(6):618–629.
Ron D, Hampton RY. Membrane biogenesis and the unfolded protein response. J Cell Biol 2004; 167(1):23–25.
Berridge MJ. The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium 2002; 32(5–6):235–249.
Sakaki K, Wu J, Kaufman RJ. Protein kinase Ctheta is required for autophagy in response to stress in the endoplasmic reticulum. J Biol Chem 2008; 283(22):15370–15380.
Szegezdi E, Logue SE, Gorman AM et al. Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 2006; 7(9):880–885.
Futami T, Miyagishi M, Taira K. Identification of a network involved in thapsigargin-induced apoptosis using a library of small interfering RNA expression vectors. J Biol Chem 2005; 280(1):826–831.
Hetz C, Thielen P, Fisher J et al. The proapoptotic BCL-2 family member BIM mediates motoneuron loss in a model of amyotrophic lateral sclerosis. Cell Death Differ 2007; 14(7):1386–1389.
Li J, Lee B, Lee AS. Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53. J Biol Chem 2006; 281(11):7260–7270.
Luo X, He Q, Huang Y et al. Transcriptional upregulation of PUMA modulates endoplasmic reticulum calcium pool depletion-induced apoptosis via Bax activation. Cell Death Differ 2005; 12(10):1310–1318.
McCullough KD, Martindale JL, Klotz LO et al. Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol Cell Biol 2001; 21(4):1249–1259.
Puthalakath H, O’Reilly LA, Gunn P et al. ER stress triggers apoptosis by activating BH3-only protein Bim. Cell 2007; 129(7):1337–1349.
Yamaguchi H, Wang HG. CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J Biol Chem 2004; 279(44):45495–45502.
Ohoka N, Yoshii S, Hattori T et al. TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. EMBO J 2005; 24(6):1243–1255.
Elyaman W, Terro F, Suen KC et al. BAD and BCL-2 regulation are early events linking neuronal endoplasmic reticulum stress to mitochondria-mediated apoptosis. Brain Res Mol Brain Res 2002; 109(1–2):233–238.
Upton JP, Austgen K, Nishino M et al. Caspase-2 cleavage of BID is a critical apoptotic signal downstream of endoplasmic reticulum stress. Mol Cell Biol 2008; 28(12):3943–3951.
Urano F, Wang X, Bertolotti A et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 2000; 287(5453):664–666.
Huang CJ, Haataja L, Gurlo T et al. Induction of endoplasmic reticulum stress-induced beta-cell apoptosis and accumulation of polyubiquitinated proteins by human islet amyloid polypeptide. Am J Physiol Endocrinol Metab 2007; 293(6):E1656–1662.
Nishitoh H, Matsuzawa A, Tobiume K et al. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev 2002; 16(11):1345–1355.
Lin JH, Li H, Yasumura D et al. IRE1 signaling affects cell fate during the unfolded protein response. Science 2007; 318(5852):944–949.
Lin JH, Li H, Zhang Y et al. Divergent effects of PERK and IRE1 signaling on cell viability. PLoS ONE 2009; 4(1):e4170.
Zinszner H, Kuroda M, Wang X et al. CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev 1998; 12(7):982–995.
Rutkowski DT, Arnold SM, Miller CN et al. Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins. PLoS Biol 2006; 4(11):e374.
Hetz C, Bernasconi P, Fisher J et al. Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha. Science 2006; 312(5773):572–576.
Papa FR, Zhang C, Shokat K et al. Bypassing a kinase activity with an ATP-competitive drug. Science 2003; 302(5650):1533–1537.
Han D, Upton JP, Hagen A et al. A kinase inhibitor activates the IRE1alpha RNase to confer cytoprotection against ER stress. Biochem Biophys Res Commun 2008; 365(4):777–783.
Klee M, Pimentel-Muinos FX. Bcl-X(L) specifically activates Bak to induce swelling and restructuring of the endoplasmic reticulum. J Cell Biol 2005; 168(5):723–734.
Aylon Y, Oren M. Living with p53, dying of p53. Cell 2007; 130(4):597–600.
Hoffman B, Liebermann DA. Apoptotic signaling by c-MYC. Oncogene 2008; 27(50):6462–6472.
Iaquinta PJ, Lees JA. Life and death decisions by the E2F transcription factors. Curr Opin Cell Biol 2007; 19(6):649–657.
Altieri DC. The case for survivin as a regulator of microtubule dynamics and cell-death decisions. Curr Opin Cell Biol 2006; 18(6):609–615.
Lamkanfi M, Festjens N, Declercq W et al. Caspases in cell survival, proliferation and differentiation. Cell Death Differ 2007; 14(1): 44–55.
Zinkel S, Gross A, Yang E. BCL2 family in DNA damage and cell cycle control. Cell Death Differ 2006; 13(8):1351–1359.
Borner C. Diminished cell proliferation associated with the death-protective activity of BCL-2. J Biol Chem 1996; 271(22):12695–12698.
Fujise K, Zhang D, Liu J et al. Regulation of apoptosis and cell cycle progression by MCL1. Differential role of proliferating cell nuclear antigen. J Biol Chem 2000; 275(50):39458–39465.
Jamil S, Sobouti R, Hojabrpour P et al. A proteolytic fragment of Mcl-1 exhibits nuclear localization and regulates cell growth by interaction with Cdk1. Biochem J 2005; 387(Pt 3):659–667.
Linette GP, Li Y, Roth K et al. Cross talk between cell death and cell cycle progression: BCL-2 regulates NFAT-mediated activation. Proc Natl Acad Sci USA 1996; 93(18):9545–9552.
Mazel S, Burtrum D, Petrie HT. Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death. J Exp Med 1996; 183(5):2219–2226.
O’Reilly LA, Huang DC, Strasser A. The cell death inhibitor BCL-2 and its homologues influence control of cell cycle entry. EMBO J 1996; 15(24):6979–6990.
Greider C, Chattopadhyay A, Parkhurst C et al. BCL-x(L) and BCL2 delay Myc-induced cell cycle entry through elevation of p27 and inhibition of G1 cyclin-dependent kinases. Oncogene 2002; 21(51):7765–7775.
Lind EF, Wayne J, Wang QZ et al. BCL-2-induced changes in E2F regulatory complexes reveal the potential for integrated cell cycle and cell death functions. J Immunol 1999; 162(9):5374–5379.
Trimarchi JM, Lees JA. Sibling rivalry in the E2F family. Nat Rev Mol Cell Biol 2002; 3(1):11–20.
Vairo G, Soos TJ, Upton TM et al. BCL-2 retards cell cycle entry through p27(Kip1), pRB relative p130 and altered E2F regulation. Mol Cell Biol 2000; 20(13):4745–4753.
Jones RG, Bui T, White C et al. The proapoptotic factors Bax and Bak regulate T-Cell proliferation through control of endoplasmic reticulum Ca(2+) homeostasis. Immunity 2007; 27(2):268–280.
Janumyan Y, Cui Q, Yan L et al. G0 function of BCL2 and BCL-xL requires BAX, BAK and p27 phosphorylation by Mirk, revealing a novel role of BAX and BAK in quiescence regulation. J Biol Chem 2008; 283(49):34108–34120.
Brady HJ, Gil-Gomez G, Kirberg J et al. Bax alpha perturbs T-cell development and affects cell cycle entry of T-cells. EMBO J 1996; 15(24):6991–7001.
Deng X, Mercer SE, Shah S et al. The cyclin-dependent kinase inhibitor p27Kip1 is stabilized in G(0) by Mirk/dyrk1B kinase. J Biol Chem 2004; 279(21):22498–22504.
Chattopadhyay A, Chiang CW, Yang E. BAD/BCL-[X(L)] heterodimerization leads to bypass of G0/G1 arrest. Oncogene 2001; 20(33):4507–4518.
Janumyan YM, Sansam CG, Chattopadhyay A et al. Bcl-xL/BCL-2 coordinately regulates apoptosis, cell cycle arrest and cell cycle entry. EMBO J 2003; 22(20):5459–5470.
Mok CL, Gil-Gomez G, Williams O et al. Bad can act as a key regulator of T-cell apoptosis and T-cell development. J Exp Med 1999; 189(3):575–586.
Uhlmann EJ, D’Sa-Eipper C, Subramanian T et al. Deletion of a nonconserved region of BCL-2 confers a novel gain of function: suppression of apoptosis with concomitant cell proliferation. Cancer Res 1996; 56(11):2506–2509.
Huang LJ, Durick K, Weiner JA et al. Identification of a novel protein kinase A anchoring protein that binds both type I and type II regulatory subunits. J Biol Chem 1997; 272(12):8057–8064.
Cheng N, Janumyan YM, Didion L et al. BCL-2 inhibition of T-cell proliferation is related to prolonged T-cell survival. Oncogene 2004; 23(21):3770–3780.
Pinton P, Rizzuto R. BCL-2 and Ca2+ homeostasis in the endoplasmic reticulum. Cell Death Differ 2006; 13(8):1409–1418.
Gottlieb E, Vander Heiden MG, Thompson CB. Bcl-x(L) prevents the initial decrease in mitochondrial membrane potential and subsequent reactive oxygen species production during tumor necrosis factor alpha-induced apoptosis. Mol Cell Biol 2000; 20(15):5680–5689.
Hockenbery DM, Oltvai ZN, Yin XM et al. BCL-2 functions in an antioxidant pathway to prevent apoptosis. Cell 1993; 75(2):241–251.
Mandal S, Guptan P, Owusu-Ansah E et al. Mitochondrial regulation of cell cycle progression during development as revealed by the tenured mutation in Drosophila. Dev Cell 2005; 9(6):843–854.
Owusu-Ansah E, Yavari A, Mandal S et al. Distinct mitochondrial retrograde signals control the G1-S cell cycle checkpoint. Nat Genet 2008; 40(3):356–361.
Hardie DG. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 2007; 8(10):774–785.
Imamura K, Ogura T, Kishimoto A et al. Cell cycle regulation via p53 phosphorylation by a 5’-AMP activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, in a human hepatocellular carcinoma cell line. Biochem Biophys Res Commun 2001; 287(2):562–567.
Jones RG, Plas DR, Kubek S et al. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 2005; 18(3):283–293.
Liang J, Shao SH, Xu ZX et al. The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat Cell Biol 2007; 9(2):218–224.
Devadas S, Zaritskaya L, Rhee SG et al. Discrete generation of superoxide and hydrogen peroxide by T-cell receptor stimulation: selective regulation of mitogen-activated protein kinase activation and fas ligand expression. J Exp Med 2002; 195(1):59–70.
Haughn L, Hawley RG, Morrison DK et al. BCL-2 and BCL-XL restrict lineage choice during hematopoietic differentiation. J Biol Chem 2003; 278(27):25158–25165.
Shibasaki F, Kondo E, Akagi T et al. Suppression of signalling through transcription factor NF-AT by interactions between calcineurin and BCL-2. Nature 1997; 386(6626):728–731.
Portier BP, Taglialatela G. BCL-2 localized at the nuclear compartment induces apoptosis after transient overexpression. J Biol Chem 2006; 281(52):40493–40502.
Fernandez-Sarabia MJ, Bischoff JR. BCL-2 associates with the ras-related protein R-ras p23. Nature 1993; 366(6452):274–275.
Chen DF, Schneider GE, Martinou JC et al. BCL-2 promotes regeneration of severed axons in mammalian CNS. Nature 1997; 385(6615):434–439.
Hilton M, Middleton G, Davies AM. BCL-2 influences axonal growth rate in embryonic sensory neurons. Curr Biol 1997; 7(10):798–800.
Sato T, Hanada M, Bodrug S et al. Interactions among members of the BCL-2 protein family analyzed with a yeast two-hybrid system. Proc Natl Acad Sci USA 1994; 91(20):9238–9242.
Zhang KZ, Westberg JA, Holtta E et al. BCL2 regulates neural differentiation. Proc Natl Acad Sci USA 1996; 93(9):4504–4508.
Jiao J, Huang X, Feit-Leithman RA et al. BCL-2 enhances Ca(2+) signaling to support the intrinsic regenerative capacity of CNS axons. EMBO J 2005; 24(5):1068–1078.
Gotz R, Wiese S, Takayama S et al. Bag1 is essential for differentiation and survival of hematopoietic and neuronal cells. Nat Neurosci 2005; 8(9):1169–1178.
Planchamp V, Bermel C, Tonges L et al. BAG1 promotes axonal outgrowth and regeneration in vivo via Raf-1 and reduction of ROCK activity. Brain 2008; 131(Pt 10):2606–2619.
Moldovan GL, Pfander B, Jentsch S. PCNA, the maestro of the replication fork. Cell 2007; 129(4):665–679.
Bartek J, Lukas C, Lukas J. Checking on DNA damage in S phase. Nat Rev Mol Cell Biol 2004; 5(10):792–804.
Shiloh Y. The ATM-mediated DNA-damage response: taking shape. Trends Biochem Sci 2006; 31(7):402–410.
Kamer I, Sarig R, Zaltsman Y et al. Proapoptotic BID is an ATM effector in the DNA-damage response. Cell 2005; 122(4):593–603.
Song G, Chen GG, Chau DK et al. Bid exhibits S phase checkpoint activation and plays a pro-apoptotic role in response to etoposide-induced DNA damage in hepatocellular carcinoma cells. Apoptosis 2008; 13(5):693–701.
Zinkel SS, Hurov KE, Ong C et al. A role for proapoptotic BID in the DNA-damage response. Cell 2005; 122(4):579–591.
Grallert B, Boye E. The multiple facets of the intra-S checkpoint. Cell Cycle 2008; 7(15):2315–2320.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Landes Bioscience and Springer Science+Business Media
About this chapter
Cite this chapter
Danial, N.N., Gimenez-Cassina, A., Tondera, D. (2010). Homeostatic Functions of BCL-2 Proteins beyond Apoptosis. In: Hetz, C. (eds) BCL-2 Protein Family. Advances in Experimental Medicine and Biology, vol 687. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6706-0_1
Download citation
DOI: https://doi.org/10.1007/978-1-4419-6706-0_1
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-6705-3
Online ISBN: 978-1-4419-6706-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)