Apoptosis

  • María Luisa Escobar
  • Gerardo H. Vázquez-Nin
  • Olga M. Echeverría
Chapter

Abstract

Cell death is a fundamental physiological process involved in controlling the balance between proliferation and differentiation during embryonic development, and in the renewal of cellular tissue throughout adulthood. It is presently known that some alterations in this process modify the cellular behavior and can lead to different pathologies, such as certain cancers and neurodegeneration processes. Apoptosis is the best studied cell death, and it is considered as programmed type I cell death. This process is characterized by several morphological cellular changes where ­cellular shrinkage, chromatin condensation, nuclear fragmentation are included. The apoptosis is executed by a group of proteases, denominated caspases, which lead to the cellular characteristics of the process.

Keywords

Flavin Adenine Dinucleotide Nuclear Localization Sequence WD40 Repeat Executer Caspases Mitochondrial Intermembrane Space 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of Abbreviations

APAF1

Apoptotic protease activating factor 1

Bak

Bcl-2 antagonist/killer

Bax

Bcl-2-associated X protein

BH3

Bcl-2-homology domain-3

Bid

BH3-interacting-domain

CARD

Caspases recruitment domain

ced-3

Caenorhabditis elegans cell-death abnormality-3

DED

Death effector domain

DISC

Death-inducing signaling complex

FADD

Fas associated death domain-containing protein

ICE

Interleukin-1 converting enzyme

Mcl-1

Myeloid cell leukemia-1

MOMP

Mitochondrial outer-membrane permeabilization

PIDD

p53-Indicible death domain

PUMA

p53-Upregulated modulator of apoptosis

Smac/DIABLO

Second mitochondrial activator of caspase/direct IAP-binding protein with low pI

tBID

Truncated BID

TNFR

TNF receptor

TNF

Tumor necrosis factor

TRADD

TNFR1-associated death domain

TRAIL

TNF-related apoptosis-inducing ligand

XIAP

X-linked inhibitor of apoptosis protein

References

  1. Acehan D, Jiang X, Morgan DG et al (2009) Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation. Mol Cell 9(2):423–432Google Scholar
  2. Adams JM, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281:1322–1326PubMedCrossRefGoogle Scholar
  3. Alnemri ES, Livingston DJ, Nicholson DW et al (1996) Human ICE/CED-3 protease nomenclature. Cell 87:171PubMedCrossRefGoogle Scholar
  4. Artus C, Boujrad H, Bouharrour A (2010) AIF promotes chromatinolysis and caspase independent programmed necrosis by interacting with histone H2AX. EMBO J 29:585–1599CrossRefGoogle Scholar
  5. Ashkenazi A, Dixit VM (1998) Death receptors: signaling and modulation. Science 281(5381):1305–1308PubMedCrossRefGoogle Scholar
  6. Boatright KM, Renatus M, Scott FL et al (2003) A unified model for apical caspase activation. Mol Cell 11:529–541PubMedCrossRefGoogle Scholar
  7. Buendia B, Santa-Maria A, Courvalin JC (1999) Caspase-dependent proteolysis of integral and peripheral proteins of nuclear membranes and nuclear pore complex proteins during apoptosis. J Cell Sci 112:1743–1753PubMedGoogle Scholar
  8. Candé C, Cecconi F, Dessen P et al (2002) Apoptosis-inducing factor (AIF): key to the conserved caspase-independent pathways of cell death? J Cell Sci 115:4727–4734PubMedCrossRefGoogle Scholar
  9. Celeste Morley S, Sun GP, Bierer BE (2003) Inhibition of actin polymerization enhances commitment to and execution of apoptosis induced by withdrawal of trophic support. J Cell Biochem 88:1066–1076PubMedCrossRefGoogle Scholar
  10. Chang HY, Yang X (2000) Proteases for cell suicide: functions and regulation of caspase. Microbiol Mol Biol Rev 64:821–846PubMedCrossRefGoogle Scholar
  11. Cheng EH, Sheiko TV, Fisher JK et al (2003) VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science 301:513–517PubMedCrossRefGoogle Scholar
  12. Cuconati A, White E (2002) Viral homologs of BCL-2: Role of apoptosis in the regulation of virus infection. Genes Dev 16:2465–2478PubMedCrossRefGoogle Scholar
  13. Delettre C, Yuste VJ, Moubarak RS et al (2006) Identification and characterization of AIFsh2, a mitochondrial apoptosis inducing factor (AIF) isoform with NADH oxidase activity. J Biol Chem 281(27):18507–18518PubMedCrossRefGoogle Scholar
  14. Earnshaw WC, Martins LM, Kaufmann SH (1999) Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 68:383–424PubMedCrossRefGoogle Scholar
  15. Eckelman BP, Salvesen GS, Scott FL (2006) Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO Rep 7:988–994PubMedCrossRefGoogle Scholar
  16. Ellis HM, Horvitz HR (1986) Genetic control of programmed cell death in the nematode C. elegans. Cell 44:817–829Google Scholar
  17. Enari M, Hug H, Nagata S (1995) Involvement of an ICE-like protease in Fas-mediated apoptosis. Nature 375:78–81PubMedCrossRefGoogle Scholar
  18. Enari M, Sakahira H, Yokoyama H et al (1998) A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 391:43–50PubMedCrossRefGoogle Scholar
  19. Fesik SW (2005) Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer 5:876–885PubMedCrossRefGoogle Scholar
  20. Fricker SP (2010) Cysteine proteases as targets for metal-based drugs. Metallomics 2:366–377PubMedCrossRefGoogle Scholar
  21. Giam M, Huang DC, Bouillet P (2008) BH3-only proteins and their roles in programmed cell death. Oncogene 27(Suppl 1):S128–S136PubMedCrossRefGoogle Scholar
  22. Gross A, McDonnell JM, Korsmeyer SJ (1999) BCL-2 family members and the mitochondria in apoptosis. Genes Dev 13:1899–1911PubMedCrossRefGoogle Scholar
  23. Gurbuxani S, Schmitt E, Cande C et al (2003) Heat shock protein 70 binding inhibits the nuclear import of apoptosis-inducing factor. Oncogene 22:6669–6678PubMedCrossRefGoogle Scholar
  24. Gyrd-Hansen M, Meier P (2010) IAPs: from caspase inhibitors to modulators of NF-κB, inflammation and cancer. Nat Rev Cancer 10(8):561–74PubMedCrossRefGoogle Scholar
  25. Huang DCS, Strasser A (2000) BH3-only proteins-essential initiators of apoptotic cell death. Cell 103:839–842PubMedCrossRefGoogle Scholar
  26. Kaufmann SH, Desnoyers S, Ottaviano Y et al (1993) Specific proteolytic cleavage of poly-(ADP-ribose) polymerase: An early marker of chemotherapy induced apoptosis. Cancer Res 53:3976–3985PubMedGoogle Scholar
  27. Kerr JF, Wyllie AH, Currie AR (1972a) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257PubMedCrossRefGoogle Scholar
  28. Kim MY, Zhang T, Kraus WL (2005) Poly(ADP-ribosyl)ation by PARP-1: ‘PAR-laying’ NAD+ into a nuclear signal. Genes Dev 19:1951–1967Google Scholar
  29. Kothakota S, Azuma T, Reinhard C et al (1997) Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis. Science 278:294–298PubMedCrossRefGoogle Scholar
  30. Kramer PH (2000) CD95’s deadly mission in the immune system. Nature 407:789–795CrossRefGoogle Scholar
  31. Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163PubMedCrossRefGoogle Scholar
  32. Kurosaka K, Takahashi M, Watanabe N et al (2003) Silent cleanup of very early apoptotic cells by macrophages. J Immunol 171:4672–4679PubMedGoogle Scholar
  33. Levee MG, Dabrowska MI, Lelli JL et al (1996) Actin polymerization and depolimerization ­during apoptosis in HL-60 cells. Am J Physiol 271:1981–1992Google Scholar
  34. Liang H, Fesik SW (1997) Three-dimensional structures of proteins involved in programmed cell death. J Mol Biol 274:291–302PubMedCrossRefGoogle Scholar
  35. Liu X, Dai S, Zhu Y et al (2003) The structure of a Bcl-xL/Bim fragment complex: Implications for Bim function. Immunity 19(3):341–352PubMedCrossRefGoogle Scholar
  36. Loeffler M, Daugas E, Susin SA et al (2001) Dominant cell death induction by extramitochondrially targeted apoptosis-inducing factor. FASEB J 15:758–767PubMedCrossRefGoogle Scholar
  37. Lu M, Lin SC, Huang Y et al (2007) XIAP induces NF-κB activation via the BIR1/TAB1 interaction and BIR1 dimerization. Mol Cell 26:689–702PubMedCrossRefGoogle Scholar
  38. Lucken-Ardjomande S, Martinou JC (2005) Regulation of Bcl-2 proteins and of the permeability of the outer mitochondrial membrane. C R Biol 328:616–631PubMedCrossRefGoogle Scholar
  39. Martin SJ, Green DR (1995) Protease activation during apoptosis: death by a thousand cuts? Cell 82:349–352PubMedCrossRefGoogle Scholar
  40. Miramar MD, Costantini P, Ravagnan L et al (2001) NADH-oxidase activity of mitochondrial apoptosis inducing factor (AIF). J Biol Chem 276:16391–16398PubMedCrossRefGoogle Scholar
  41. Modjtahedi N, Giordanetto F, Madeo F et al (2006) Apoptosis-inducing factor: vital and lethal. Trends Cell Biol 16:264–272PubMedCrossRefGoogle Scholar
  42. Montague JW, Hughes FM Jr, Cidlowski JA (1997) Native recombinant cyclophilins A, B, and C degrade DNA independently of peptidylprolyl cistrans-isomerase activity. Potential roles of cyclophilins in apoptosis. J Biol Chem 272(10):6677–6684Google Scholar
  43. Muzio M, Chinnaiyan AM, Kischkel FC et al (1996) FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. Cell 85:817–827PubMedCrossRefGoogle Scholar
  44. Muzio M, Stockwell BR, Stennicke HR et al (1998) An induced proximity model for caspase-8 activation. J Biol Chem 273(5):2926–2930Google Scholar
  45. Nagata S (1997) Apoptosis by death factor. Cell 88:355–365PubMedCrossRefGoogle Scholar
  46. Nagata S, Goldstein P (1995) The Fas death factor. Science 267:1449–1456PubMedCrossRefGoogle Scholar
  47. Nakagawa T, Yuan J (2000) Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J Cell Biol 150:887–894PubMedCrossRefGoogle Scholar
  48. Nakagawa T, Zhu H, Morishima N et al (2000) Caspase-12 mediates endoplasmic reticulum-­specific apoptosis and cytotoxicity by amyloid-b. Nature 403:98–103PubMedCrossRefGoogle Scholar
  49. Otera H, Ohsakaya S, Nagaura Z et al (2005) Export of mitochondrial AIF in response to proapoptotic stimuli depends on processing at the intermembrane space. EMBO J 24:1375–1386PubMedCrossRefGoogle Scholar
  50. Prior FP, Salvesen SG (2004) The protein structures that shape caspase activity, specificity, activation and inhibition. Biochem J 384:201–232CrossRefGoogle Scholar
  51. Ramage P, Cheneval D, Chvei M et al (1995) Expression, refolding, and autocatalytic proteolytic processing of the interleukin-1 beta-converting enzyme precursor. J Biol Chem 270:9378–9383PubMedCrossRefGoogle Scholar
  52. Ravagnan L, Roumier T, Kroemer G (2002) Mitochondria-the killer organelles and their weapons. J Cell Physiol 192:131–137PubMedCrossRefGoogle Scholar
  53. Read SH, Baliga BC, Ekert P et al (2002) A novel Apaf-1-independent putative caspase-2 activation complex. J Cell Biol 159(5):739–745Google Scholar
  54. Ried SJ, Salvesen GS (2007) The apoptosome: signalling platform of cell death. Nat Rev Mol Cell Biol 8:405–413CrossRefGoogle Scholar
  55. Ried SJ, Li W, Chao Y et al (2005) Structure of the apoptotic protease-activating factor 1 bound to ADP. Nature 434:926–933CrossRefGoogle Scholar
  56. Riento K, Ridley AJ (2003) Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol 4:446–456PubMedCrossRefGoogle Scholar
  57. Rodriguez J, Lazebnik Y (1999) Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev 13:3179–3184PubMedCrossRefGoogle Scholar
  58. Rudel T, Bokoch GM (1997) Membrane and morphological changes in apoptotic cells regulated by caspase-mediated activation of PAK2. Science 276:1571–1574PubMedCrossRefGoogle Scholar
  59. Rupinder SK, Gurpreet AK, Manjeet S (2007) Cell suicide and caspases. Vasc Pharmacol 46:383–393CrossRefGoogle Scholar
  60. Salvesen GS, Dixit VM (1999) Caspase activation: the induced-proximity model. Proc Natl Acad Sci USA 96:10964–10967PubMedCrossRefGoogle Scholar
  61. Sandu C, Morisawa G, Wegorzewska I et al (2006) FADD self-association is required for stable interaction with an activated death receptor. Cell Death Differ 13:2052–2061PubMedCrossRefGoogle Scholar
  62. Sattler M, Liang H, Nettesheim D et al (1997) Structure of Bcl-xL-Bak peptide complex: Recognition between regulators of apoptosis. Science 275:983–986PubMedCrossRefGoogle Scholar
  63. Savill J, Fadok V (2000) Corpse clearance defines the meaning of cell death. Nature 407:784–788PubMedCrossRefGoogle Scholar
  64. Schneider P, Tschopp J (2000) Apoptosis induced by death receptors. Pharm Acta Helv 74:281–286PubMedGoogle Scholar
  65. Scott FL, Denault JB, Ried SJ et al (2005) XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs. EMBO J 24:645–655PubMedCrossRefGoogle Scholar
  66. Shiozaki EN, Chai J, Rigotti DJ et al (2003) Mechanism of XIAP-mediated inhibition of ­caspase-9. Mol Cell 11:519–527PubMedCrossRefGoogle Scholar
  67. Stegh AH, Peter ME (2001) Apoptosis and caspases. Cardiol Clin 19:13–29PubMedCrossRefGoogle Scholar
  68. Stennicke HR, Salvesen GS (1999) Catalytic properties of the caspases. Cell Death Differ 6:1054–1059PubMedCrossRefGoogle Scholar
  69. Sun C, Cai M, Gunasekera AH et al (1999) NMR structure and mutagenesis of the inhibitor-of-apoptosis protein XIAP. Nature 401:818–822PubMedCrossRefGoogle Scholar
  70. Susin SA, Lorenzo HK, Zamzami N et al (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397:441–446PubMedCrossRefGoogle Scholar
  71. Suzuki M, Youle RJ, Tjandra N (2000) Structure of Bax: Coregulation of dimer formation and intracellular localization. Cell 103:645–654PubMedCrossRefGoogle Scholar
  72. Tinel A, Tschopp J (2004) The PIDDosome, a protein complex implicated in activation of ­caspase-2 in response to genotoxic stress. Science 304:843–846PubMedCrossRefGoogle Scholar
  73. Tosello-Trampont AC, Nakada-Tsukui K, Ravichandran KS (2003) Engulfment of apoptotic cells is negatively regulated by Rho-mediated signaling. J Biol Chem 278:49911–49919PubMedCrossRefGoogle Scholar
  74. Upton JP, Valentijn AJ, Zhang L et al (2007) The N-terminal conformation of Bax regulates cell commitment to apoptosis. Cell Death Differ 14:932–942PubMedGoogle Scholar
  75. Valentijn AJ, Metcalfe AD, Kott J et al (2003) Spatial and temporal changes in Bax subcellular localization during anoikis. J Cell Biol 162:599–612PubMedCrossRefGoogle Scholar
  76. Vaux DL, Silke J (2005) IAPs, RINGs and ubiquitylation. Nat Rev Mol Cell Biol 6:287–297PubMedCrossRefGoogle Scholar
  77. Wei MC, Zong WX, Cheng EH (2001) Proapoptotic BAX and BAK: A requisite gateway to mitochondrial dysfunction and death. Science 292:727–730PubMedCrossRefGoogle Scholar
  78. Wen LP, Fahrni JA, Troie S et al (1997) Cleavage of focal adhesion kinase by caspases during apoptosis. J Biol Chem 272:26056–26061PubMedCrossRefGoogle Scholar
  79. Willis SN, Fletcher JI, Kaufmann T et al (2007) Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 315:856–859PubMedCrossRefGoogle Scholar
  80. Wyllie AH (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284:555–556PubMedCrossRefGoogle Scholar
  81. Yamin TT, Ayala JM, Miller DK (1996) Activation of the native 45-kDa precursor form of ­interleukin-1-converting enzyme. J Biol Chem 271:13273–13282PubMedCrossRefGoogle Scholar
  82. Yang Y, Fang S, Jensen JP et al (2000) Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science 28:874–877CrossRefGoogle Scholar
  83. Yuste VJ, Moubarak RS, Delettre C et al (2005) Cysteine protease inhibition prevents mitochondrial apoptosis-inducing factor (AIF) release. Cell Death Differ 12:1445–1448PubMedCrossRefGoogle Scholar
  84. Zhu C, Wang X, Deinum J (2007) Cyclophilin A participates in the nuclear translocation of apoptosis-inducing factor in neurons after cerebral hypoxia-ischemia. J Exp Med 204:1741–1748PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • María Luisa Escobar
    • 1
  • Gerardo H. Vázquez-Nin
    • 1
  • Olga M. Echeverría
    • 1
  1. 1.Laboratory of Electron Microscopy, Department of Cell Biology, Faculty of SciencesNational University of Mexico (UNAM)MexicoUSA

Personalised recommendations