Cited by 1,366Cell death mechanisms and regulationAutophagy in Disease and TherapyDeath, Funerary Practices, and Mourning

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Crosstalk between apoptosis.; necrosis and autophagy

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Nikoletopoulou, Vassiliki, Markaki, Maria, Palikaras, Konstantinos, Tavernarakis, Nektarios·2013·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

DOI 10.1016/j.bbamcr.2013.06.001

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Abstract

Apoptosis and necrosis are the two major modes of cell death, the molecular mechanisms of which have been extensively studied. Although initially thought to constitute mutually exclusive cellular states, recent findings reveal cellular contexts that require a balanced interplay between these two modes of cellular demise. Several death initiator and effector molecules, signaling pathways and subcellular sites have been identified as key mediators in both processes, either by constituting common modules or alternatively by functioning as a switch allowing cells to decide which route to take, depending on the specific situation. Importantly, autophagy, which is a predominantly cytoprotective process, has been linked to both types of cell death, serving either a pro-survival or pro-death function. Here we review the recent literature that highlights the intricate interplay between apoptosis, necrosis and autophagy, focusing on the relevance and impact of this crosstalk in normal development and in pathology. This article is part of a Special Section entitled: Cell Death Pathways.

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Role of poly(ADP-ribose) synthetase in inflammation and ischaemia–reperfusion
Szabó, C., & Dawson, V. L. (1998) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(98)01193-6 · Cited by 685 · cited 1×
“PARP1 over-activation consumes large amounts of NAD+, resulting in a massive ATP depletion [51,52].”
Background
The mitochondrial p53 pathway
Vaseva, A. V., & Moll, U. M. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.10.005 · Cited by 634 · cited 1×
“Upon stress, a cytoplasmic pool of p53 rapidlytranslocatestothemitochondrialsurface,whereit physically interacts with both anti-and pro-apoptotic BCL-2 family members to inhibit or activate their respective functions, leading to MOMP and apoptosis [57].”
Background
Alkylating DNA damage stimulates a regulated form of necrotic cell deathPreprint
Zong, W., Ditsworth, D., Bauer, D. E., Wang, Z., & Thompson, C. B. (2004) · Genes & Development · doi:10.1101/gad.1199904 · Cited by 618 · cited 1×
“PARP1 over-activation leads to ATP depletion, thereby inducing necrotic cell death and preventing energy-dependent apoptosis [7,28,133].”
Background
Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL
Shimizu, S., Eguchi, Y., Kosaka, H., Kamiike, W., Matsuda, H., & Tsujimoto, Y. (1995) · Nature · doi:10.1038/374811a0 · Cited by 611 · cited 1×
“Moreover, overexpression of BCL-2 was also found sufficient to prevent the necrotic death of neuronal [70] and non-neuronal cells [71].”
Background
RIP Kinase-Dependent Necrosis Drives Lethal Systemic Inflammatory Response Syndrome
Duprez, L., Takahashi, N., Hauwermeiren, F. V., Vandendriessche, B., Goossens, V., Berghe, T. V., Declercq, W., Libert, C., Cauwels, A., & Vandenabeele, P. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.020 · Cited by 607 · cited 1×
“Moreover, it was recently demonstrated that RIP kinase-dependent necrosis drives TNF-induced systemic inflammatory response syndrome [47].”
Background
DAP‐kinase‐mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl‐XL and induction of autophagy
Zalckvar, E., Berissi, H., Mizrachy, L., Idelchuk, Y., Koren, I., Eisenstein, M., Sabanay, H., Pinkas‐Kramarski, R., & Kimchi, A. (2009) · The EMBO Reports · doi:10.1038/embor.2008.246 · Cited by 592 · cited 2×
“DAPK-mediated phosphorylation of Beclin 1 on Thr119 at the BH3 domain promotes the dissociation of Beclin 1 from its inhibitor BCL-2-family members, thereby activating Beclin 1 to induce autophagy [110].”
Background
Calcium, mitochondria and reperfusion injury: a pore way to die
Halestrap, A. P. (2006) · Biochemical Society Transactions · doi:10.1042/bst20060232 · Cited by 561 · cited 1×
“Necrosis in ischemic tissues depends on cyclophilin D (CypD), the key regulator of the mitochondrial permeability transition pore (PTP) at the inner membrane, whose opening leads to cell death [59].”
Background
Dual Signaling of the Fas Receptor: Initiation of Both Apoptotic and Necrotic Cell Death Pathways
Vercammen, D., Brouckaert, G., Denecker, G., Van de Craen, M., Declercq, W., Fiers, W., & Vandenabeele, P. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.5.919 · Cited by 556
Distinct p53 Transcriptional Programs Dictate Acute DNA-Damage Responses and Tumor Suppression
Brady, C. A., Jiang, D., Mello, S. S., Johnson, T. M., Jarvis, L. A., Kozak, M. M., Broz, D. K., Basak, S., Park, E. J., McLaughlin, M. E., et al. (2011) · Cell · doi:10.1016/j.cell.2011.03.035 · Cited by 533 · cited 1×
“In turn, it controls programs of apoptosis typically by inducing the transcription of components of the death receptor and mitochondrial pathways suchasCD95,PUMA,NOXA, BAX, and others,whichact cooperatively to promote cell death [53,54].”
Background
Activation and Caspase-mediated Inhibition of PARP: A Molecular Switch between Fibroblast Necrosis and Apoptosis in Death Receptor Signaling
Łoś, M., Mozoluk, M., Ferrari, D., Stępczyńska, A., Stroh, C., Renz, A., Herceg, Z., Wang, Z., & Schulze‐Osthoff, K. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-05-0272 · Cited by 505 · cited 19×
“PARP1 over-activation leads toATPdepletion,therebyinducing necrotic cell death and preventing energy-dependent apoptosis [7,28,133].”
BackgroundInfluential
Apoptosis blocks Beclin 1-dependent autophagosome synthesis: an effect rescued by Bcl-xL
Luo, S., & Rubinsztein, D. C. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.121 · Cited by 495 · cited 1×
“The ﬁ nding that the pro-apoptotic protein BAX reduces autophagy by enhancing caspase-mediated cleavage of Beclin 1 at D149 and the fact that non-caspase cleavable Beclin 1, as well as, BCL-X L can rescue BAX-induced autophagy, indicates that apoptosis can suppress autophagy [102].”
Background
Differential Effects of Endoplasmic Reticulum Stress-induced Autophagy on Cell Survival
Ding, W., Ni, H., Gao, W., Hou, Y., Melan, M. A., Chen, X., Stolz, D. B., Shao, Z.-M., & Yin, X. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m609267200 · Cited by 494 · cited 1×
“non-transformed murine embryonic fibroblasts, autophagy does not alleviate ER stress but rather contributes to ER-induced apoptosis [82].”
Background
DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death
Inbal, B., Bialik, S., Sabanay, I., Shani, G., & Kimchi, A. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200109094 · Cited by 481 · cited 1×
“The role of DAPK in the regulation of autophagy has been established in mammalian cell culture [108] and in C. elegans , where downregulation of dapk - 1 , the worm ortholog of DAPK, by mutation or RNAi knockdown reduces starvation-induced autophagy in the pharyngeal muscles [109].”
Background
Apoptosis-inducing factor is involved in the regulation of caspase-independent neuronal cell death
Cregan, S. P., Fortin, A., MacLaurin, J. G., Callaghan, S. M., Cecconi, F., Yu, S.-W., Dawson, T. M., Dawson, V. L., Park, D. S., Kroemer, G., et al. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200202130 · Cited by 478 · cited 1×
“Chemical inhibition or genetic ablation of PARP1, as well as of AIF prevent DNA-damage-induced death, [73,74,80] further demonstrating the absolute requirement of PARP1 and AIF in necroptosis.”
Background
RIP1, a kinase on the crossroads of a cell's decision to live or die
Festjens, N., Berghe, T. V., Cornelis, S., & Vandenabeele, P. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402085 · Cited by 467
A Role for Tumor Necrosis Factor Receptor-2 and Receptor-interacting Protein in Programmed Necrosis and Antiviral Responses
Chan, F. K.-M., Shisler, J. L., Bixby, J. G., Felices, M., Zheng, L., APPEL, M. C., Orenstein, J. O., Moss, B., & Lenardo, M. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305633200 · Cited by 463 · cited 2×
“Although it has long been known that viruses encode anti-apoptotic proteins to prevent their host cells from killing themselves by apoptosis, this work also demonstrates that viruses harbor proteins that suppress programmed necrosis [19].”
Background
The Death-Associated Protein Kinases: Structure, Function, and Beyond
Bialik, S., & Kimchi, A. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142615 · Cited by 447
FLIP-mediated autophagy regulation in cell death control
Lee, J.-S., Li, Q., Lee, J.-Y., Lee, S.-H., Jeong, J. H., Lee, H.-R., Chang, H., Zhou, F.-C., Gao, S.-J., Liang, C., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1980 · Cited by 406 · cited 1×
“Collectively, FLIPs act not only as anti-apoptotic factors but also as suppressors of autophagy through their inhibitory interaction with ATG3[105].”
Background
Bioenergetic aspects of apoptosis, necrosis and mitoptosis
Skulachev, V. P. (2006) · APOPTOSIS · doi:10.1007/s10495-006-5881-9 · Cited by 391
Caspase-independent cell death in T lymphocytes
Jäättelä, M., & Tschopp, J. (2003) · Nature Immunology · doi:10.1038/ni0503-416 · Cited by 373 · cited 1×
“This type of programmed cell death is controlled by mitochondria and its major effector is the mitochondrial protein AIF [77,78].”
Background
TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation
Jouan-Lanhouet, S., Arshad, M. I., Piquet-Pellorce, C., Martin-Chouly, C., Le Moigne-Muller, G., Van Herreweghe, F., Takahashi, N., Sergent, O., Lagadic-Gossmann, D., Vandenabeele, P., et al. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2012.90 · Cited by 357 · cited 2×
“In line with this, in the mousemodelofConA-inducedhepatitis,wheredeathofmousehepato-cytes is dependent on TRAIL, PARP1 activity was positively correlated with liver injury and hepatitis [21].”
Background
Apoptotic Cell Death Triggered by Nitric Oxide in Pancreatic β-Cells
Kaneto, H., Fujii, J., Seo, H. G., Suzuki, K., Matsuko, T.-A., Masahiro, N., Tatsumi, H., Yamasaki, Y., Kamada, T., & Taniguchi, N. (1995) · Diabetes · doi:10.2337/diab.44.7.733 · Cited by 342
Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking
Zeng, X., Overmeyer, J. H., & Maltese, W. A. (2006) · Journal of Cell Science · doi:10.1242/jcs.02735 · Cited by 339
Survival Function of the FADD-CASPASE-8-cFLIPL Complex
Dillon, C. P., Oberst, A., Weinlich, R., Janke, L. J., Kang, T.-B., Ben-Moshe, T., Mak, T. W., Wallach, D., & Green, D. R. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.03.010 · Cited by 331 · cited 1×
“Deregulation of either pathway during development results in embryonic lethality [42].”
Background
Sequential Activation of Poly(ADP-Ribose) Polymerase 1, Calpains, and Bax Is Essential in Apoptosis-Inducing Factor-Mediated Programmed Necrosis
Moubarak, R. S., Yuste, V. J., Artus, C., Bouharrour, A., Greer, P. A., Murcia, J. M., & Susín, S. A. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02141-06 · Cited by 322 · cited 16×
“This necroptotic process, which is also regulated by the kinase RIP1[73] is executed by the activation of PARP1, Ca 2+ -dependent calpain Cys-proteases, and the pro-apoptotic BAX [74].”
BackgroundInfluential
Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance
Bonapace, L., Bornhauser, B. C., Schmitz, M., Cario, G., Ziegler, U., Niggli, F. K., Schäfer, B. W., Schrappe, M., Stanulla, M., & Bourquin, J. (2010) · Journal of Clinical Investigation · doi:10.1172/jci39987 · Cited by 320 · cited 1×
“The molecular underpinnings of this relationship remain largely elusive and somewhat controversial; autophagy has been shown to either promote [120], suppress [121,122] or not link with necroptosis [123].”
Background
FADD and caspase-8 control the outcome of autophagic signaling in proliferating T cells
Bell, B. D., Leverrier, S., Weist, B. M., Newton, R. H., Arechiga, A. F., Luhrs, K. A., Morrissette, N. S., & Walsh, C. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808597105 · Cited by 300 · cited 2×
“The molecular underpinnings of this relationship remain largely elusive and somewhat controversial; autophagy has been shown to either promote [120], suppress [121,122] or not link with necroptosis [123].”
Background
PRAS40 and PRR5-Like Protein Are New mTOR Interactors that Regulate Apoptosis
Thedieck, K., Polak, P., Kim, M. L., Molle, K. D., Cohen, A., Jenö, P., Arrieumerlou, C., & Hall, M. N. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001217 · Cited by 300 · cited 1×
“Recently, two new mTOR interactors have been identi ﬁ ed, the proline-rich AKT substrate (PRAS40) and the protein Q6MZQ0/FLJ14213/CAE45978, which appear to be implicated in the regulation of apoptosis, thereby controlling the balance between cell growth and cell death [90].”
Background
The Adaptor Protein FADD Protects Epidermal Keratinocytes from Necroptosis In Vivo and Prevents Skin Inflammation
Bonnet, M. C., Preukschat, D., Welz, P.-S., van Loo, G., Ermolaeva, M. A., Bloch, W., Haase, I., & Pasparakis, M. (2011) · Immunity · doi:10.1016/j.immuni.2011.08.014 · Cited by 295
Dual roles of autophagy in the survival of Caenorhabditis elegans during starvation
Kang, C., You, Y.-J., & Avery, L. (2007) · Genes & Development · doi:10.1101/gad.1573107 · Cited by 294 · cited 1×
“The role of DAPK in the regulation of autophagy has been established in mammalian cell culture [108] and in C. elegans , where downregulation of dapk - 1 , the worm ortholog of DAPK, by mutation or RNAi knockdown reduces starvation-induced autophagy in the pharyngeal muscles [109].”
Background
The Sirtuin family: therapeutic targets to treat diseases of aging
Milne, J. C., & Denu, J. M. (2008) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2008.01.019 · Cited by 274 · cited 1×
“Sirtuins are NAD + -dependent protein deacetylases, involved in the regulation of a number of processes including transcription, apoptosis, stress resistance and ageing [127].”
Background
DAP-kinase is a mediator of endoplasmic reticulum stress-induced caspase activation and autophagic cell death
Gözüaçık, D., Bialik, S., Raveh, T., Mitou, G., Shohat-Ophir, G., Sabanay, H., Mizushima, N., Yoshimori, T., & Kimchi, A. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.121 · Cited by 266 · cited 1×
“The ﬁ nding that both apoptosis and autophagy are attenuated in these experimental settings, supports the view that DAPK integrates signals from apoptotic and autophagy pathways to induce cell death during ER stress [107].”
Background
Caspase cleavage of Atg4D stimulates GABARAP-L1 processing and triggers mitochondrial targeting and apoptosis
Betin, V. M. S., & Lane, J. D. (2009) · Journal of Cell Science · doi:10.1242/jcs.046250 · Cited by 261 · cited 1×
“Interestingly, overexpression of caspase-cleaved ATG4D induces apoptosis in human cells that is preceded by the rapid recruitment of ATG4D to mitochondria [103].”
Background
PARP-1 is involved in autophagy induced by DNA damage
Muñoz‐Gámez, J. A., Rodríguez-Vargas, J. M., Quiles, R., Aguilar‐Quesada, R., Martín‐Oliva, D., de MURCIA, G., Murcia, J. M., Almendros-Ruiz, A., de Almodóvar, J. M. R., & Oliver, F. J. (2009) · Autophagy · doi:10.4161/auto.5.1.7272 · Cited by 253
Activation of the PI3K-Akt-mTOR signaling pathway promotes necrotic cell death via suppression of autophagy
Wu, Y., Tan, H., Huang, Q. B., Ong, C. N., & Shen, H. (2009) · Autophagy · doi:10.4161/auto.9099 · Cited by 241 · cited 1×
“The pro-survival function of autophagy in zVAD-induced necroptosis is also highlighted by the observation that inhibition of autophagy via the mTOR signaling pathway enhances necroptosis, while starvation protects against zVAD-induced necroptotic cell death [86,124 – 126].”
Background
Poly(ADP-ribose) Polymerase-1 Signaling to Mitochondria in Necrotic Cell Death Requires RIP1/TRAF2-mediated JNK1 Activation
Xu, Y., Huang, S., Liu, Z. G., & Han, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m508135200 · Cited by 235 · cited 17×
“Recent work performed in mouse embryonic ﬁ - broblastsindicatesthatinadditiontoRIP1andRIP3,theadaptorprotein FADD is also crucial for TNF α -induced necroptosis, while the formation of TNF α -induced RIP1-RIP3 necroptotic complex is independent of cytosolic Ca 2+ [36].”
BackgroundInfluential
Bax/Bak-Dependent Release of DDP/TIMM8a Promotes Drp1-Mediated Mitochondrial Fission and Mitoptosis during Programmed Cell Death
Arnoult, D., Rismanchi, N., Grodet, A., Roberts, R. G., Seeburg, D. P., Estaquier, J., Sheng, M., & Blackstone, C. D. (2005) · Current Biology · doi:10.1016/j.cub.2005.10.041 · Cited by 234 · cited 1×
“This interaction activates Drp1-mediated mitochondrial fission and subsequently mitoptosis [116].”
Background
Mammalian Target of Rapamycin (mTOR): Pro- and Anti-Apoptotic
Castedo, M., Ferri, K. F., & Kroemer, G. (2002) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400978 · Cited by 230 · cited 1×
“…cytoplasmic vacuolization, which could lead to autophagic cell death [86 – 88]. mTOR has been reported to have pleiotropic effects on apoptosis that are most likely dependent on the cellular context as well as diverse downstream targets, such as p53, BAD and BCL-2 proteins, among others [89].”
Background
Inactivation of the Autophagy Gene bec-1 Triggers Apoptotic Cell Death in C. elegans
Takács‐Vellai, K., Vellai, T., Puoti, A., Passannante, M., Wicky, C., Streit, A., Kovács, A. L., & Müller, F. (2005) · Current Biology · doi:10.1016/j.cub.2005.07.035 · Cited by 228 · cited 2×
“It is welldocumented that the crosstalk between autophagy and apoptosis is mediated at least in part by the functional and structural interaction between Beclin 1 and the anti-apoptotic proteins BCL-2 and BCL-XL [96,97].”
Background
Protein Kinase Cδ Selectively Regulates Protein Kinase D-Dependent Activation of NF-κB in Oxidative Stress Signaling
Störz, P., Döppler, H. R., & Toker, A. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.7.2614-2626.2004 · Cited by 227
Expression of bcl‐2 inhibits necrotic neural cell death
Kane, D. J., Örd, T., Anton, R., & Bredesen, D. E. (1995) · Journal of Neuroscience Research · doi:10.1002/jnr.490400216 · Cited by 212 · cited 1×
“Moreover, overexpression of BCL-2 was also found suf ﬁ cient to prevent the necrotic death of neuronal [70] and non-neuronal cells [71].”
Background
Poly(ADP-ribose) polymerase inhibitors preserve oxidized nicotinamide adenine dinucleotide and adenosine 5'-triphosphate pools in DNA-damaged cells: mechanism of stimulation of unscheduled DNA synthesis
Sims, J. L., Berger, S. J., & Berger, N. A. (1983) · Biochemistry · doi:10.1021/bi00291a019 · Cited by 199 · cited 1×
“PARP1 over-activation consumes large amounts of NAD+, resulting in a massive ATP depletion [51,52].”
Background
Induction of interferon-γ production in Th1 CD4+ T cells: evidence for two distinct pathways for promoter activation
Yang, J., Murphy, T. L., Ouyang, W., & MURPHY, K. M. M. (1999) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199902)29:02 · Cited by 195
AIF‐mediated caspase‐independent necroptosis: A new chance for targeted therapeutics
Delavallée, L., Cabon, L., Galán‐Malo, P., Lorenzo, H. K., & Susín, S. A. (2011) · IUBMB Life · doi:10.1002/iub.432 · Cited by 189 · cited 1×
“N-methyl-N0-nitro-N0-nitrosoguanidine (MNNG) [72].”
Bcl-2 complexed with Beclin-1 maintains full anti-apoptotic function
Ciechomska, I. A., Goemans, G. C., Skepper, J. N., & Tolkovsky, A. M. (2009) · Oncogene · doi:10.1038/onc.2009.60 · Cited by 186 · cited 1×
“The fact that binding of Beclin 1 to BCL-2 does not modify apoptosis even in autophagy-de ﬁ cient Atg5 − / − mouse embryonic ﬁ - broblasts (MEF) argues against a protective role for Beclin 1-mediated autophagy [100].”
Background
Molecular Basis of Bcl-xL’s Target Recognition Versatility Revealed by the Structure of Bcl-xL in Complex with the BH3 Domain of Beclin-1
Feng, W., Huang, S., Wu, H., & Zhang, M. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.06.069 · Cited by 184 · cited 1×
“In complex II, RIP1 and RIP3 are inactivated by proteolytic cleavage by caspase-8, thereby initiating the pro-apoptotic caspase activation cascade [28,32].”
Background
Mitochondrial effectors in caspase‐independent cell death
Lorenzo, H. K., & Susín, S. A. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)01464-9 · Cited by 178 · cited 1×
“This type of programmed cell death is controlled by mitochondria and its major effector is the mitochondrial protein AIF [77,78].”
Background
zVAD-induced necroptosis in L929 cells depends on autocrine production of TNFα mediated by the PKC–MAPKs–AP-1 pathway
Wu, Y., Tan, H.-L., Huang, Q., Xj, S., Zhu, X., & Shen, H.-M. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.72 · Cited by 176
AIF-Mediated Programmed Necrosis: A Highly Orchestrated Way to Die
Boujrad, H., Gubkina, O., Robert, N., Krantic, S. M., & Susín, S. A. (2007) · Cell Cycle · doi:10.4161/cc.6.21.4842 · Cited by 165 · cited 2×
“1) has been introduced to describe cases where death with apoptotic features, such as nuclear chromatin condensation morphology takes place in a caspase-independent manner [76].”
Background
Cytokines Induce Both Necrosis and Apoptosis via a Common Bcl-2-Inhibitable Pathway in Rat Insulin-Producing Cells*
Saldeen, J. (2000) · Endocrinology · doi:10.1210/endo.141.6.7523 · Cited by 160 · cited 1×
“Using the rat insulin-producing β -cell line RINm5F, it was shown that both apoptosis and necrosis of these cells, induced by treatment with various cytokines, could be prevented by overexpression of BCL-2 [69].”
Background
Autophagy plays a protective role during zVAD-induced necrotic cell death
Wu, Y., Tan, H., Huang, Q., Kim, Y.-S., Pan, N., Ong, W., Liu, Z.-G., Ong, C. N., & Shen, H. (2008) · Autophagy · doi:10.4161/auto.5662 · Cited by 159
MCL‐1 is a stress sensor that regulates autophagy in a developmentally regulated manner
Germain, M., Nguyen, A. P., Le Grand, J. N., Arbour, N., Vanderluit, J. L., Park, D. S., Opferman, J. T., & Slack, R. S. (2011) · The EMBO Journal · doi:10.1038/emboj.2010.327 · Cited by 159 · cited 1×
“Consistent with the potential role for TOR in modulating both autophagy and apoptosis, mTOR inhibition following nutrient deprivation has been suggested to cause MCL1 degradation [91].”
Background
Fas-associated death domain (FADD) is a negative regulator of T-cell receptor–mediated necroptosis
Osborn, S. L., Diehl, G. E., Han, S., Xue, L., Kurd, N. S., Hsieh, K., Cado, D., Robey, E. A., & Winoto, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005997107 · Cited by 156 · cited 1×
“The molecular underpinnings of this relationship remain largely elusive and somewhat controversial; autophagy has been shown to either promote [120], suppress [121,122] or not link with necroptosis [123].”
Background
Mitochondrial phosphoglycerate mutase 5 uses alternate catalytic activity as a protein serine/threonine phosphatase to activate ASK1
Takeda, K., Komuro, Y., Hayakawa, T., Oguchi, H., Ishida, Y., Murakami, S., Noguchi, T., Kinoshita, H., Sekine, Y., Iemura, S.-I., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0901823106 · Cited by 147 · cited 1×
“Inte-restingly, PGAM5, a mitochondrial phosphoglyceratemutase, was also recently reported to associate with the necrosome, providing a potential point of convergence for increased mitochondrial ﬁ ssion and necroptosis ([40,41]; reviewed in [37]).”
Background
The selectivity of autophagy and its role in cell death and survival
Yu, L., Strandberg, L., & Lenardo, M. (2008) · Autophagy · doi:10.4161/auto.5902 · Cited by 144 · cited 1×
“…of autophagy upon nutrient replenishment and as such prevents excess cytoplasmic vacuolization, which could lead to autophagic cell death [86 – 88]. mTOR has been reported to have pleiotropic effects on apoptosis that are most likely dependent on the cellular context as well as diverse…”
Background
BID regulates AIF-mediated caspase-independent necroptosis by promoting BAX activation
Cabon, L., Galán‐Malo, P., Bouharrour, A., Delavallée, L., Brunelle-Navas, M.-N., Lorenzo, H. K., Gross, A., & Susín, S. A. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.91 · Cited by 139 · cited 1×
“Cleaved into tBID via a calpain cleavage at Gly70, this BH3-only protein is indeed the link between calpains and BAX in MNNG-mediated necroptosis [75].”
Background
PKD is a kinase of Vps34 that mediates ROS-induced autophagy downstream of DAPk
Eisenberg‐Lerner, A., & Kimchi, A. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.149 · Cited by 137 · cited 2×
“Interestingly, PKD acts downstream of DAPK, with both of them required to induce autophagy under oxidative stress [147].”
Background
Cytokine-induced apoptotic cell death in a mouse pancreatic beta-cell line: inhibition by Bcl-2
Iwahashi, H., Hanafusa, T., Eguchi, Y., Nakajima, H., Miyagawa, J.-I., Itoh, N., Tomita, K., Namba, M., Kuwajima, M., Noguchi, T., et al. (1996) · Diabetologia · doi:10.1007/bf00403299 · Cited by 132
Upgrading the BCL-2 Network
Galonek, H. L., & Hardwick, J. M. (2006) · Nature Cell Biology · doi:10.1038/ncb1206-1317 · Cited by 128 · cited 1×
“BH3 domains can bind to BH3 receptors and inhibit the anti-apoptotic BCL-2 proteins, such as BCL-2 and BCL-X L , or activate the pro-apoptotic BCL-2 family members, such as BAX and BAK [99].”
Background
The p53-cathepsin axis cooperates with ROS to activate programmed necrotic death upon DNA damage
Tu, H.-C., Ren, D., Wang, G. X., Chen, D. Y., Westergard, T. D., Kim, H., Sasagawa, S., Hsieh, J. J.-D., & Cheng, E. H. Y. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808173106 · Cited by 126 · cited 2×
“In contrast,H 2 O 2 -induced necrosis in double knockout MEFs was found to be completely transcription independent [58].”
Background
Autophagy and Caspases: A New Cell Death Program
Li, Y., Lenardo, M. J., & Baehrecke, E. H. (2004) · Cell Cycle · doi:10.4161/cc.3.9.1097 · Cited by 124
Novel mechanism of elimination of malfunctioning mitochondria (mitoptosis): Formation of mitoptotic bodies and extrusion of mitochondrial material from the cell
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“…have indicated that elimination of malfunctioning mitochondria may occur either through autophagosome formation via selective mitochondrial autophagy (mitophagy) [117] or through the formation of mitoptotic bodies, which are then released into the extracellular space via atypical exocytosis [118].”
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Oxidative Stress Induces Protein Kinase D Activation in Intact Cells
Waldron, R. T., & Rozengurt, E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m908959199 · Cited by 120 · cited 1×
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PI3K/AKT inhibition induces caspase-dependent apoptosis in HTLV-1-transformed cells
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To die or to live: the dual role of poly(ADP-ribose) polymerase-1 in autophagy and necrosis under oxidative stress and DNA damage
Huang, Q. B., & Shen, H. (2009) · Autophagy · doi:10.4161/auto.5.2.7640 · Cited by 108
Requirement of FADD, NEMO, and BAX/BAK for Aberrant Mitochondrial Function in Tumor Necrosis Factor Alpha-Induced Necrosis
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DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress
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“The molecular underpinnings of this relationship remain largely elusive and somewhat controversial; autophagy has been shown to either promote [120], suppress [121,122] or not link with necroptosis [123].”
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AIFsh, a Novel Apoptosis-inducing Factor (AIF) Pro-apoptotic Isoform with Potential Pathological Relevance in Human Cancer
Delettre, C., Yuste, V. J., Moubarak, R. S., Bras, M., Lesbordes, J.-C., Pêtres, S., Bellalou, J., & Susín, S. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509884200 · Cited by 90
New components of the necroptotic pathway
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“Inte-restingly, PGAM5, a mitochondrial phosphoglyceratemutase, was also recently reported to associate with the necrosome, providing a potential point of convergence for increased mitochondrial ﬁ ssion and necroptosis ([40,41]; reviewed in [37]).”
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Akt Regulates TNFα Synthesis Downstream of RIP1 Kinase Activation during Necroptosis
McNamara, C. R., Ahuja, R., Osafo-Addo, A. D., Barrows, D., Kettenbach, A. N., Skidan, I. N., Teng, X., Cuny, G. D., Gerber, S. A., & Degterev, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056576 · Cited by 69
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“Autophagy and necrosis: the involvement of the DAPK – PKD pathway PKD (Protein Kinase D1) is a serine/threonine kinase involved in many cellular processes such as cell proliferation, cell motility and cell death [142], and is activated upon oxidative stress [143,144].”
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Expression of the bcl-2 Gene from a Defective HSV-1 Amplicon Vector Protects Pancreatic β -Cells from Apoptosis
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Mitoptosis, a Novel Mitochondrial Death Mechanism Leading Predominantly to Activation of Autophagy
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Anti-neoplastic activity of the cytosolic FoxO1 results from autophagic cell death
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BAX/BAK–Independent Mitoptosis during Cell Death Induced by Proteasome Inhibition?
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Changes in poly(ADP-ribose) level modulate the kinetics of DNA strand break rejoining
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Caspase inhibition in apoptotic T cells triggers necrotic cell death depending on the cell type and the proapoptotic stimulus
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Background
PARP-1 inhibition induces a late increase in the level of reactive oxygen species in cells after ionizing radiation
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Mouse embryonic stem cells undergo charontosis, a novel programmed cell death pathway dependent upon cathepsins, p53, and EndoG, in response to etoposide treatment
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Nitric Oxide Rather than Superoxide or Peroxynitrite Inhibits Insulin Secretion and Causes DNA Damage in HIT-T15 Cells
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“cesses [220].”
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Authors: Nikoletopoulou, V., Markaki, M., Palikaras, K., & Tavernarakis, N.
Affiliations: Foundation for Research and Technology Hellas (GR)
Corresponding author: Tavernarakis, Nektarios
ORCID: Nikoletopoulou, Vassiliki
Markaki, Maria
Palikaras, Konstantinos
Tavernarakis, Nektarios
Venue: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Publisher: Elsevier BV
Published: 2013-12
Volume: 1833
Issue: 12
Pages: 3448-3459
ISSN: 0167-4889 (ISSN-L)
DOI: 10.1016/j.bbamcr.2013.06.001
OpenAlex: W2059738518
Cited by: 1,366
References: 150
Citations by year: 2026: 43 · 2025: 58 · 2024: 80 · 2023: 91 · 2022: 113 · 2021: 147 · 2020: 133 · 2019: 146 · 2018: 136 · 2017: 141 · 2016: 122 · 2015: 107 · 2014: 43 · 2013: 5
FWCI: 8.50
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 365 d)
Locations: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (publishedVersion)
PubMed (publishedVersion)
IRIS (submittedVersion)
SERVAL (Université de Lausanne) (submittedVersion)
Funders: European Research Council
Ministry of National Education and Religious Affairs
European Molecular Biology Organization
Seventh Framework Programme
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Social Sciences › Anthropology › Death, Funerary Practices, and Mourning
Keywords: apoptosis, necrosis, autophagy, cell death crosstalk, cell death pathways, cell fate determination, development (biology), disease pathology
MeSH terms: Autophagy, Humans, Models, Biological, Necrosis, Signal Transduction, Apoptosis

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Crosstalk between apoptosis.; necrosis and autophagy

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