Abstract
In this review, we discuss the signal-transduction pathways of three major cellular responses induced by tumor necrosis factor (TNF): cell survival through NF-κB activation, apoptosis, and necrosis. Recruitment and activation of caspases plays a crucial role in the initiation and execution of TNF-induced apoptosis. However, experimental inhibition of caspases reveals an alternative cell death pathway, namely necrosis, also called necroptosis, suggesting that caspases actively suppress the latter outcome. TNF-induced necrotic cell death crucially depends on the kinase activity of receptor interacting protein serine-threonine kinase 1 (RIP1) and RIP3. It was recently demonstrated that ubiquitination of RIP1 determines whether it will function as a pro-survival or pro-cell death molecule. Deeper insight into the mechanisms that control the molecular switches between cell survival and cell death will help us to understand why TNF can exert so many different biological functions in the etiology and pathogenesis of human diseases.
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References
Clarke PG (1990) Developmental cell death: morphological diversity and multiple mechanisms. Anat Embryol (Berl) 181:195–213
Kerr JF (1971) Shrinkage necrosis: a distinct mode of cellular death. J Pathol 105:13–20
Schweichel JU, Merker HJ (1973) The morphology of various types of cell death in prenatal tissues. Teratology 7:253–266
Fimia GM, Piacentini M (2010) Regulation of autophagy in mammals and its interplay with apoptosis. Cell Mol Life Sci (in press, this issue)
Bortoluci KR, Medzhitov R (2010) Control of infection by pyroptosis and autophagy. Cell Mol Life Sci (in press, this issue)
Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487–501
Balkwill F (2009) Tumour necrosis factor and cancer. Nat Rev Cancer 9:361–371
Wilson NS, Dixit V, Ashkenazi A (2009) Death receptor signal transducers: nodes of coordination in immune signaling networks. Nat Immunol 10:348–355
Johnstone RW, Frew AJ, Smyth MJ (2008) The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer 8:782–798
Kelliher MA, Grimm S, Ishida Y, Kuo F, Stanger BZ, Leder P (1998) The death domain kinase RIP mediates the TNF-induced NF-kappaB signal. Immunity 8:297–303
Wong WW-L, Gentle IE, Carter H, Vaux DL, Silke J (2010) RIPK1 is not essential for TNFR1 induced activation of NF-κB. Cell Death Differ 17:482–487
O’Donnell MA, Legarda-Addison D, Skountzos P, Yeh WC, Ting AT (2007) Ubiquitination of RIP1 regulates an NF-kappaB-independent cell-death switch in TNF signaling. Curr Biol 17:418–424
Wang L, Du F, Wang X (2008) TNF-alpha induces two distinct caspase-8 activation pathways. Cell 133:693–703
Festjens N, Vanden Berghe T, Cornelis S, Vandenabeele P (2007) RIP1, a kinase on the crossroads of a cell’s decision to live or die. Cell Death Differ 14:400–410
Sun X, Yin J, Starovasnik MA, Fairbrother WJ, Dixit VM (2002) Identification of a novel homotypic interaction motif required for the phosphorylation of receptor-interacting protein (RIP) by RIP3. J Biol Chem 277:9505–9511
Newton K, Sun X, Dixit VM (2004) Kinase RIP3 is dispensable for normal NF-kappa Bs, signaling by the B-cell and T-cell receptors, tumor necrosis factor receptor 1, and Toll-like receptors 2 and 4. Mol Cell Biol 24:1464–1469
Degterev A, Hitomi J, Germscheid M, Ch’en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J (2008) Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 4:313–321
Micheau O, Tschopp J (2003) Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 114:181–190
Schneider-Brachert W, Tchikov V, Neumeyer J, Jakob M, Winoto-Morbach S, Held-Feindt J, Heinrich M, Merkel O, Ehrenschwender M, Adam D, Mentlein R, Kabelitz D, Schutze S (2004) Compartmentalization of TNF receptor 1 signaling: internalized TNF receptosomes as death signaling vesicles. Immunity 21:415–428
Adam-Klages S, Adam D, Wiegmann K, Struve S, Kolanus W, Schneider-Mergener J, Kronke M (1996) FAN, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral sphingomyelinase. Cell 86:937–947
Werneburg N, Guicciardi ME, Yin XM, Gores GJ (2004) TNF-alpha-mediated lysosomal permeabilization is FAN and caspase 8/Bid dependent. Am J Physiol Gastrointest Liver Physiol 287:G436–G443
Legarda-Addison D, Hase H, O’Donnell MA, Ting AT (2009) NEMO/IKKgamma regulates an early NF-kappaB-independent cell-death checkpoint during TNF signaling. Cell Death Differ 16:1279–1288
Luo X, Budihardjo I, Zou H, Slaughter C, Wang X (1998) Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94:481–490
Pradelli LA, Bénéteau M, Ricci JE (2010) Mitochondrial control of caspase dependent and -independent cell death. Cell Mol Life Sci (this issue, in press)
Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB, Korsmeyer SJ (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292:727–730
Chipuk JE, Green DR (2008) How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol 18:157–164
Amsel AD, Rathaus M, Kronman N, Cohen HY (2008) Regulation of the proapoptotic factor Bax by Ku70-dependent deubiquitylation. Proc Natl Acad Sci USA 105:5117–5122
Lalier L, Cartron PF, Juin P, Nedelkina S, Manon S, Bechinger B, Vallette FM (2007) Bax activation and mitochondrial insertion during apoptosis. Apoptosis 12:887–896
Ross K, Rudel T, Kozjak-Pavlovic V (2009) TOM-independent complex formation of Bax and Bak in mammalian mitochondria during TNFalpha-induced apoptosis. Cell Death Differ 16:697–707
Ott M, Norberg E, Walter KM, Schreiner P, Kemper C, Rapaport D, Zhivotovsky B, Orrenius S (2007) The mitochondrial TOM complex is required for tBid/Bax-induced cytochrome c release. J Biol Chem 282:27633–27639
Lutter M, Fang M, Luo X, Nishijima M, Xie X, Wang X (2000) Cardiolipin provides specificity for targeting of tBid to mitochondria. Nat Cell Biol 2:754–761
Ardail D, Privat JP, Egret-Charlier M, Levrat C, Lerme F, Louisot P (1990) Mitochondrial contact sites. Lipid composition and dynamics. J Biol Chem 265:18797–18802
Gonzalvez F, Schug ZT, Houtkooper RH, MacKenzie ED, Brooks DG, Wanders RJ, Petit PX, Vaz FM, Gottlieb E (2008) Cardiolipin provides an essential activating platform for caspase-8 on mitochondria. J Cell Biol 183:681–696
Lovell JF, Billen LP, Bindner S, Shamas-Din A, Fradin C, Leber B, Andrews DW (2008) Membrane binding by tBid initiates an ordered series of events culminating in membrane permeabilization by Bax. Cell 135:1074–1084
Riedl SJ, Salvesen GS (2007) The apoptosome: signalling platform of cell death. Nat Rev Mol Cell Biol 8:405–413
Riedl SJ, Li W, Chao Y, Schwarzenbacher R, Shi Y (2005) Structure of the apoptotic protease-activating factor 1 bound to ADP. Nature 434:926–933
Shi Y (2004) Caspase activation: revisiting the induced proximity model. Cell 117:855–858
Chao Y, Shiozaki EN, Srinivasula SM, Rigotti DJ, Fairman R, Shi Y (2005) Engineering a dimeric caspase-9: a re-evaluation of the induced proximity model for caspase activation. PLoS Biol 3:e183
Lee TH, Shank J, Cusson N, Kelliher MA (2004) The kinase activity of Rip1 is not required for tumor necrosis factor-alpha-induced IkappaB kinase or p38 MAP kinase activation or for the ubiquitination of Rip1 by Traf2. J Biol Chem 279:33185–33191
Ea CK, Deng L, Xia ZP, Pineda G, Chen ZJ (2006) Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol Cell 22:245–257
Ermolaeva MA, Michallet MC, Papadopoulou N, Utermohlen O, Kranidioti K, Kollias G, Tschopp J, Pasparakis M (2008) Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF-dependent inflammatory responses. Nat Immunol 9:1037–1046
Tada K, Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, Hashimoto H, Mak TW, Yagita H, Okumura K, Yeh WC, Nakano H (2001) Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death. J Biol Chem 276:36530–36534
Wu CJ, Conze DB, Li X, Ying SX, Hanover JA, Ashwell JD (2005) TNF-alpha induced c-IAP1/TRAF2 complex translocation to a Ubc6-containing compartment and TRAF2 ubiquitination. EMBO J 24:1886–1898
Mahoney DJ, Cheung HH, Mrad RL, Plenchette S, Simard C, Enwere E, Arora V, Mak TW, Lacasse EC, Waring J, Korneluk RG (2008) Both cIAP1 and cIAP2 regulate TNFalpha-mediated NF-kappaB activation. Proc Natl Acad Sci USA 105:11778–11783
Bertrand MJ, Milutinovic S, Dickson KM, Ho WC, Boudreault A, Durkin J, Gillard JW, Jaquith JB, Morris SJ, Barker PA (2008) cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell 30:689–700
Kanayama A, Seth RB, Sun L, Ea CK, Hong M, Shaito A, Chiu YH, Deng L, Chen ZJ (2004) TAB 2 and TAB 3 activate the NF-kappaB pathway through binding to polyubiquitin chains. Mol Cell 15:535–548
Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412:346–351
Verstrepen L, Bekaert T, Chau TL, Tavernier J, Chariot A, Beyaert R (2008) TLR-4, IL-1R, and TNF-R signaling to NF-kappaB: variations on a common theme. Cell Mol Life Sci 65:2964–2978
Wertz IE, O’Rourke KM, Zhou H, Eby M, Aravind L, Seshagiri S, Wu P, Wiesmann C, Baker R, Boone DL, Ma A, Koonin EV, Dixit VM (2004) De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature 430:694–699
Zhang SQ, Kovalenko A, Cantarella G, Wallach D (2000) Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation. Immunity 12:301–311
Shembade N, Harhaj NS, Parvatiyar K, Copeland NG, Jenkins NA, Matesic LE, Harhaj EW (2008) The E3 ligase Itch negatively regulates inflammatory signaling pathways by controlling the function of the ubiquitin-editing enzyme A20. Nat Immunol 9:254–262
Enesa K, Zakkar M, Chaudhury H, le Luong A, Rawlinson L, Mason JC, Haskard DO, Dean JL, Evans PC (2008) NF-kappaB suppression by the deubiquitinating enzyme Cezanne: a novel negative feedback loop in pro-inflammatory signaling. J Biol Chem 283:7036–7045
Liao W, Xiao Q, Tchikov V, Fujita K, Yang W, Wincovitch S, Garfield S, Conze D, El-Deiry WS, Schutze S, Srinivasula SM (2008) CARP-2 is an endosome-associated ubiquitin ligase for RIP and regulates TNF-induced NF-kappaB activation. Curr Biol 18:641–649
Sun SC (2010) CYLD: a tumor suppressor deubiquitinase regulating NF-kappaB activation and diverse biological processes. Cell Death Differ 17:25–34
Wright A, Reiley WW, Chang M, Jin W, Lee AJ, Zhang M, Sun SC (2007) Regulation of early wave of germ cell apoptosis and spermatogenesis by deubiquitinating enzyme CYLD. Dev Cell 13:705–716
Dempsey PW, Doyle SE, He JQ, Cheng G (2003) The signaling adaptors and pathways activated by TNF superfamily. Cytokine Growth Factor Rev 14:193–209
Cortes Sempere M, Rodriguez Fanjul V, Sanchez Perez I, Perona R (2008) The role of the NFkappaB signalling pathway in cancer. Clin Transl Oncol 10:143–147
Chang DW, Xing Z, Capacio VL, Peter ME, Yang X (2003) Interdimer processing mechanism of procaspase-8 activation. EMBO J 22:4132–4142
Micheau O, Thome M, Schneider P, Holler N, Tschopp J, Nicholson DW, Briand C, Grutter MG (2002) The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex. J Biol Chem 277:45162–45171
Kataoka T, Tschopp J (2004) N-terminal fragment of c-FLIP(L) processed by caspase 8 specifically interacts with TRAF2 and induces activation of the NF-kappaB signaling pathway. Mol Cell Biol 24:2627–2636
Safa AR, Day TW, Wu CH (2008) Cellular FLICE-like inhibitory protein (C-FLIP): a novel target for cancer therapy. Curr Cancer Drug Targets 8:37–46
Srinivasula SM, Ashwell JD (2008) IAPs: what’s in a name? Mol Cell 30:123–135
Callus BA, Vaux DL (2007) Caspase inhibitors: viral, cellular and chemical. Cell Death Differ 14:73–78
Huang Y, Park YC, Rich RL, Segal D, Myszka DG, Wu H (2001) Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain. Cell 104:781–790
Eckelman BP, Salvesen GS, Scott FL (2006) Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO Rep 7:988–994
Shiozaki EN, Chai J, Rigotti DJ, Riedl SJ, Li P, Srinivasula SM, Alnemri ES, Fairman R, Shi Y (2003) Mechanism of XIAP-mediated inhibition of caspase-9. Mol Cell 11:519–527
Shiozaki EN, Shi Y (2004) Caspases, IAPs and Smac/DIABLO: mechanisms from structural biology. Trends Biochem Sci 29:486–494
Chai J, Du C, Wu JW, Kyin S, Wang X, Shi Y (2000) Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Nature 406:855–862
Gao Z, Tian Y, Wang J, Yin Q, Wu H, Li YM, Jiang X (2007) A dimeric Smac/diablo peptide directly relieves caspase-3 inhibition by XIAP. Dynamic and cooperative regulation of XIAP by Smac/Diablo. J Biol Chem 282:30718–30727
Vogler M, Walczak H, Stadel D, Haas TL, Genze F, Jovanovic M, Bhanot U, Hasel C, Moller P, Gschwend JE, Simmet T, Debatin KM, Fulda S (2009) Small molecule XIAP inhibitors enhance TRAIL-induced apoptosis and antitumor activity in preclinical models of pancreatic carcinoma. Cancer Res 69:2425–2434
Eckelman BP, Salvesen GS (2006) The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases. J Biol Chem 281:3254–3260
Choi YE, Butterworth M, Malladi S, Duckett CS, Cohen GM, Bratton SB (2009) The E3 ubiquitin ligase cIAP1 binds and ubiquitinates caspases-3 and -7 via unique mechanisms at distinct steps in their processing. J Biol Chem 284:12772–12782
Li L, Thomas RM, Suzuki H, De Brabander JK, Wang X, Harran PG (2004) A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death. Science 305:1471–1474
Vince JE, Wong WW, Khan N, Feltham R, Chau D, Ahmed AU, Benetatos CA, Chunduru SK, Condon SM, McKinlay M, Brink R, Leverkus M, Tergaonkar V, Schneider P, Callus BA, Koentgen F, Vaux DL, Silke J (2007) IAP antagonists target cIAP1 to induce TNFalpha-dependent apoptosis. Cell 131:682–693
Leist M, Single B, Castoldi AF, Kuhnle S, Nicotera P (1997) Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med 185:1481–1486
Festjens N, Vanden Berghe T, Vandenabeele P (2006) Necrosis, a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response. Biochim Biophys Acta 1757:1371–1387
Fiers W, Beyaert R, Declercq W, Vandenabeele P (1999) More than one way to die: apoptosis, necrosis and reactive oxygen damage. Oncogene 18:7719–7730
Vanlangenakker N, Berghe TV, Krysko DV, Festjens N, Vandenabeele P (2008) Molecular mechanisms and pathophysiology of necrotic cell death. Curr Mol Med 8:207–220
Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, Bodmer JL, Schneider P, Seed B, Tschopp J (2000) Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol 1:489–495
Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N, Cuny GD, Mitchison TJ, Moskowitz MA, Yuan J (2005) Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol 1:112–119
Xu Y, Huang S, Liu ZG, Han J (2006) Poly(ADP-ribose) polymerase-1 signaling to mitochondria in necrotic cell death requires RIP1/TRAF2-mediated JNK1 activation. J Biol Chem 281:8788–8795
Lim SY, Davidson SM, Mocanu MM, Yellon DM, Smith CC (2007) The cardioprotective effect of necrostatin requires the cyclophilin-D component of the mitochondrial permeability transition pore. Cardiovasc Drugs Ther 21:467–469
Bogan KL, Brenner C (2008) Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu Rev Nutr 28:115–130
Eliasson MJ, Sampei K, Mandir AS, Hurn PD, Traystman RJ, Bao J, Pieper A, Wang ZQ, Dawson TM, Snyder SH, Dawson VL (1997) Poly (ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nat Med 3:1089–1095
Fraser H, Lopaschuk GD, Clanachan AS (1998) Assessment of glycogen turnover in aerobic, ischemic, and reperfused working rat hearts. Am J Physiol 275:H1533–H1541
Matthews N (1983) Anti-tumour cytotoxin produced by human monocytes: studies on its mode of action. Br J Cancer 48:405–410
Hitomi J, Christofferson DE, Ng A, Yao J, Degterev A, Xavier RJ, Yuan J (2008) Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell 135:1311–1323
Temkin V, Huang Q, Liu H, Osada H, Pope RM (2006) Inhibition of ADP/ATP exchange in receptor-interacting protein-mediated necrosis. Mol Cell Biol 26:2215–2225
He S, Wang L, Miao L, Wang T, Du F, Zhao L, Wang X (2009) Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell 137:1100–1111
Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC, Dong MQ, Han J (2009) RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325:332–336
Declercq W, Vanden Berghe T, Vandenabeele P (2009) RIP kinases at the crossroads of cell death and survival. Cell 138:229–232
Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, Chan FK (2009) Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137:1112–1123
Schulze-Osthoff K, Bakker AC, Vanhaesebroeck B, Beyaert R, Jacob WA, Fiers W (1992) Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation. J Biol Chem 267:5317–5323
Andreyev AY, Kushnareva YE, Starkov AA (2005) Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc) 70:200–214
Goossens V, Stange G, Moens K, Pipeleers D, Grooten J (1999) Regulation of tumor necrosis factor-induced, mitochondria- and reactive oxygen species-dependent cell death by the electron flux through the electron transport chain complex I. Antioxid Redox Signal 1:285–295
Festjens N, Kalai M, Smet J, Meeus A, Van Coster R, Saelens X, Vandenabeele P (2006) Butylated hydroxyanisole is more than a reactive oxygen species scavenger. Cell Death Differ 13:166–169
Goossens V, Grooten J, Fiers W (1996) The oxidative metabolism of glutamine. A modulator of reactive oxygen intermediate-mediated cytotoxicity of tumor necrosis factor in L929 fibrosarcoma cells. J Biol Chem 271:192–196
Vannucci RC, Brucklacher RM, Vannucci SJ (2005) Glycolysis and perinatal hypoxic-ischemic brain damage. Dev Neurosci 27:185–190
Xiong ZG, Zhu XM, Chu XP, Minami M, Hey J, Wei WL, MacDonald JF, Wemmie JA, Price MP, Welsh MJ, Simon RP (2004) Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels. Cell 118:687–698
Gandhi S, Wood-Kaczmar A, Yao Z, Plun-Favreau H, Deas E, Klupsch K, Downward J, Latchman DS, Tabrizi SJ, Wood NW, Duchen MR, Abramov AY (2009) PINK1-associated Parkinson’s disease is caused by neuronal vulnerability to calcium-induced cell death. Mol Cell 33:627–638
Odagiri K, Katoh H, Kawashima H, Tanaka T, Ohtani H, Saotome M, Urushida T, Satoh H, Hayashi H (2009) Local control of mitochondrial membrane potential, permeability transition pore and reactive oxygen species by calcium and calmodulin in rat ventricular myocytes. J Mol Cell Cardiol 46:989–997
Dumas JF, Argaud L, Cottet-Rousselle C, Vial G, Gonzalez C, Detaille D, Leverve X, Fontaine E (2009) Effect of transient and permanent permeability transition pore opening on NAD(P)H localization in intact cells. J Biol Chem 284:15117–15125
Juhaszova M, Wang S, Zorov DB, Nuss HB, Gleichmann M, Mattson MP, Sollott SJ (2008) The identity and regulation of the mitochondrial permeability transition pore: where the known meets the unknown. Ann N Y Acad Sci 1123:197–212
Palma E, Tiepolo T, Angelin A, Sabatelli P, Maraldi NM, Basso E, Forte MA, Bernardi P, Bonaldo P (2009) Genetic ablation of cyclophilin D rescues mitochondrial defects and prevents muscle apoptosis in collagen VI myopathic mice. Hum Mol Genet 18:2024–2031
Schnitzer E, Pinchuk I, Lichtenberg D (2007) Peroxidation of liposomal lipids. Eur Biophys J 36:499–515
Kim C, Kim JY, Kim JH (2008) Cytosolic phospholipase A(2), lipoxygenase metabolites, and reactive oxygen species. BMB Rep 41:555–559
Burke JE, Dennis EA (2009) Phospholipase A2 biochemistry. Cardiovasc Drugs Ther 23:49–59
Diez E, Louis-Flamberg P, Hall RH, Mayer RJ (1992) Substrate specificities and properties of human phospholipases A2 in a mixed vesicle model. J Biol Chem 267:18342–18348
Hirabayashi T, Murayama T, Shimizu T (2004) Regulatory mechanism and physiological role of cytosolic phospholipase A2. Biol Pharm Bull 27:1168–1173
Suffys P, Beyaert R, De Valck D, Vanhaesebroeck B, Van Roy F, Fiers W (1991) Tumour-necrosis-factor-mediated cytotoxicity is correlated with phospholipase-A2 activity, but not with arachidonic acid release per se. Eur J Biochem 195:465–475
Strelow A, Bernardo K, Adam-Klages S, Linke T, Sandhoff K, Kronke M, Adam D (2000) Overexpression of acid ceramidase protects from tumor necrosis factor-induced cell death. J Exp Med 192:601–612
Ramos B, Lahti JM, Claro E, Jackowski S (2003) Prevalence of necrosis in C2-ceramide-induced cytotoxicity in NB16 neuroblastoma cells. Mol Pharmacol 64:502–511
Jayadev S, Hayter HL, Andrieu N, Gamard CJ, Liu B, Balu R, Hayakawa M, Ito F, Hannun YA (1997) Phospholipase A2 is necessary for tumor necrosis factor alpha-induced ceramide generation in L929 cells. J Biol Chem 272:17196–17203
Won JS, Singh I (2006) Sphingolipid signaling and redox regulation. Free Radic Biol Med 40:1875–1888
Poppe M, Reimertz C, Munstermann G, Kogel D, Prehn JH (2002) Ceramide-induced apoptosis of D283 medulloblastoma cells requires mitochondrial respiratory chain activity but occurs independently of caspases and is not sensitive to Bcl-xL overexpression. J Neurochem 82:482–494
Llacuna L, Mari M, Garcia-Ruiz C, Fernandez-Checa JC, Morales A (2006) Critical role of acidic sphingomyelinase in murine hepatic ischemia-reperfusion injury. Hepatology 44:561–572
Shimizu M, Tada E, Makiyama T, Yasufuku K, Moriyama Y, Fujino H, Nakamura H, Murayama T (2009) Effects of ceramide, ceramidase inhibition and expression of ceramide kinase on cytosolic phospholipase A2alpha; additional role of ceramide-1-phosphate in phosphorylation and Ca2+ signaling. Cell Signal 21:440–447
Hinkovska-Galcheva V, VanWay SM, Shanley TP, Kunkel RG (2008) The role of sphingosine-1-phosphate and ceramide-1-phosphate in calcium homeostasis. Curr Opin Investig Drugs 9:1192–1205
Kar P, Chakraborti T, Samanta K, Chakraborti S (2009) mu-Calpain mediated cleavage of the Na+/Ca2+ exchanger in isolated mitochondria under A23187 induced Ca2+ stimulation. Arch Biochem Biophys 482:66–76
Liu Z, Wang S, Zhou H, Yang Y, Zhang M (2009) Na+/H+ exchanger mediates TNF-alpha-induced hepatocyte apoptosis via the calpain-dependent degradation of Bcl-xL. J Gastroenterol Hepatol 24:879–885
Toyota H, Yanase N, Yoshimoto T, Moriyama M, Sudo T, Mizuguchi J (2003) Calpain-induced Bax-cleavage product is a more potent inducer of apoptotic cell death than wild-type Bax. Cancer Lett 189:221–230
Chua BT, Guo K, Li P (2000) Direct cleavage by the calcium-activated protease calpain can lead to inactivation of caspases. J Biol Chem 275:5131–5135
Lee WK, Abouhamed M, Thevenod F (2006) Caspase-dependent and -independent pathways for cadmium-induced apoptosis in cultured kidney proximal tubule cells. Am J Physiol Renal Physiol 291:F823–F832
Impens F, Van Damme P, Demol H, Van Damme J, Vandekerckhove J, Gevaert K (2008) Mechanistic insight into taxol-induced cell death. Oncogene 27:4580–4591
Bano D, Young KW, Guerin CJ, Lefeuvre R, Rothwell NJ, Naldini L, Rizzuto R, Carafoli E, Nicotera P (2005) Cleavage of the plasma membrane Na+/Ca2+ exchanger in excitotoxicity. Cell 120:275–285
Syntichaki P, Xu K, Driscoll M, Tavernarakis N (2002) Specific aspartyl and calpain proteases are required for neurodegeneration in C. elegans. Nature 419:939–944
Harwood SM, Allen DA, Raftery MJ, Yaqoob MM (2007) High glucose initiates calpain-induced necrosis before apoptosis in LLC-PK1 cells. Kidney Int 71:655–663
Yamashima T, Tonchev AB, Tsukada T, Saido TC, Imajoh-Ohmi S, Momoi T, Kominami E (2003) Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates. Hippocampus 13:791–800
Oikawa S, Yamada T, Minohata T, Kobayashi H, Furukawa A, Tada-Oikawa S, Hiraku Y, Murata M, Kikuchi M, Yamashima T (2009) Proteomic identification of carbonylated proteins in the monkey hippocampus after ischemia-reperfusion. Free Radic Biol Med 46:1472–1477
Boya P, Kroemer G (2008) Lysosomal membrane permeabilization in cell death. Oncogene 27:6434–6451
Syntichaki P, Samara C, Tavernarakis N (2005) The vacuolar H+-ATPase mediates intracellular acidification required for neurodegeneration in C. elegans. Curr Biol 15:1249–1254
Xie C, Zhang N, Zhou H, Li J, Li Q, Zarubin T, Lin SC, Han J (2005) Distinct roles of basal steady-state and induced H-ferritin in tumor necrosis factor-induced death in L929 cells. Mol Cell Biol 25:6673–6681
Zhao M, Antunes F, Eaton JW, Brunk UT (2003) Lysosomal enzymes promote mitochondrial oxidant production, cytochrome c release and apoptosis. Eur J Biochem 270:3778–3786
Droga-Mazovec G, Bojic L, Petelin A, Ivanova S, Romih R, Repnik U, Salvesen GS, Stoka V, Turk V, Turk B (2008) Cysteine cathepsins trigger caspase-dependent cell death through cleavage of bid and antiapoptotic Bcl-2 homologues. J Biol Chem 283:19140–19150
Kurz T, Terman A, Gustafsson B, Brunk UT (2008) Lysosomes and oxidative stress in aging and apoptosis. Biochim Biophys Acta 1780:1291–1303
Ono K, Wang X, Han J (2001) Resistance to tumor necrosis factor-induced cell death mediated by PMCA4 deficiency. Mol Cell Biol 21:8276–8288
Ono K, Kim SO, Han J (2003) Susceptibility of lysosomes to rupture is a determinant for plasma membrane disruption in tumor necrosis factor alpha-induced cell death. Mol Cell Biol 23:665–676
Acknowledgments
We thank Amin Bredan for editing the manuscript. FVH is funded by a Postdoc grant from APO-SYS, FP7. NF is a postdoctoral fellow of FWO (Fonds Wetenschappelijk Onderzoek–Vlaanderen), PV and WD are research professors at the Ghent University. This work has been supported by Flanders Institute for Biotechnology (VIB) and several grants from the European Union (EC Marie Curie Training and Mobility Program, FP6, ApopTrain, MRTN-CT-035624; EC RTD Integrated Project, FP6, Epistem, LSHB-CT-2005-019067, APO-SYS, FP7, HEALTH-F4-2007-200767), the Interuniversity Poles of Attraction-Belgian Science Policy (IAP6/18), the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (G.0133.05 and 3G.0218.06), and the Special Research Fund of Ghent University (Geconcerteerde Onderzoekstacties 12.0505.02). PV is holder of a Methusalem grant from the Flemish government.
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Van Herreweghe, F., Festjens, N., Declercq, W. et al. Tumor necrosis factor-mediated cell death: to break or to burst, that’s the question. Cell. Mol. Life Sci. 67, 1567–1579 (2010). https://doi.org/10.1007/s00018-010-0283-0
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DOI: https://doi.org/10.1007/s00018-010-0283-0