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Apoptosis-inducing factor (AIF) and leukocyte elastase inhibitor/l-DNase II (LEI/LDNaseII), can interact to conduct caspase-independent cell death

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Abstract

Programmed cell death is an important factor in tissue homeostasis. Lot of work has been performed to characterize the caspase-dependent cell death. Caspase-independent cell death, although important in many physiological situations, is less investigated. In this work we show that two caspase-independent effectors of cell death, namely apoptosis-inducing factor and leukocyte elastase inhibitor derived DNase II interact and can cooperate to induce cell death. These results contribute to the knowledge of molecular pathways of cell death, an important issue in the development of new therapeutic strategies for the treatment of cancer or neurodegenerative diseases.

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References

  1. Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV et al (2012) Molecular definitions of cell death subroutines: recommendations of the nomenclature committee on cell death 2012. Cell Death Differ 19:107–120

    Article  PubMed  CAS  Google Scholar 

  2. Boujrad H, Gubkina O, Robert N, Krantic S, Susin SA (2007) AIF-mediated programmed necrosis: a highly regulated way to die. Cell Cycle 6:2612–2619

    Article  PubMed  CAS  Google Scholar 

  3. Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM et al (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397:441–446

    Article  PubMed  CAS  Google Scholar 

  4. Dawson VL, Dawson TM (2004) Deadly conversations: nuclear-mitochondrial cross-talk. J Bioenerg Biomembr 36:287–294

    Article  PubMed  CAS  Google Scholar 

  5. Moubarak RS, Yuste VJ, Artus C, Bouharrour A, Greer PA, Menissier-de Murcia J et al (2007) Sequential activation of poly(ADP-ribose) polymerase 1, calpains, and Bax is essential in apoptosis-inducing factor-mediated programmed necrosis. Mol Cell Biol 27:4844–4862

    Article  PubMed  CAS  Google Scholar 

  6. Mate MJ, Ortiz-Lombardia M, Boitel B, Haouz A, Tello D, Susin SA et al (2002) The crystal structure of the mouse apoptosis-inducing factor AIF. Nat Struct Biol 9:442–446

    Article  PubMed  CAS  Google Scholar 

  7. Delavallee L, Cabon L, Galan-Malo P, Lorenzo HK, Susin SA (2011) AIF-mediated caspase-independent necroptosis: a new chance for targeted therapeutics. IUBMB Life 63:221–232

    Article  PubMed  CAS  Google Scholar 

  8. Joza N, Oudit GY, Brown D, Benit P, Kassiri Z, Vahsen N et al (2005) Muscle-specific loss of apoptosis-inducing factor leads to mitochondrial dysfunction, skeletal muscle atrophy, and dilated cardiomyopathy. Mol Cell Biol 25:10261–10272

    Article  PubMed  CAS  Google Scholar 

  9. Klein JA, Longo-Guess CM, Rossmann MP, Seburn KL, Hurd RE, Frankel WN et al (2002) The harlequin mouse mutation down regulates apoptosis-inducing factor. Nature 419:367–374

    Article  PubMed  CAS  Google Scholar 

  10. Wang H, Yu SW, Koh DW, Lew J, Coombs C, Bowers W et al (2004) Apoptosis-inducing factor substitutes for caspase executioners in NMDA-triggered excitotoxic neuronal death. J Neurosci 24:10963–10973

    Article  PubMed  CAS  Google Scholar 

  11. Delettre C, Yuste VJ, Moubarak RS, Bras M, Lesbordes-Brion JC, Petres S et al (2006) AIFsh, a novel apoptosis-inducing factor (AIF) pro-apoptotic isoform with potential pathological relevance in human cancer. J Biol Chem 281:6413–6427

    Article  PubMed  CAS  Google Scholar 

  12. Ishitsuka K, Hideshima T, Hamasaki M, Raje N, Kumar S, Podar K et al (2005) Novel inosine monophosphate dehydrogenase inhibitor VX-944 induces apoptosis in multiple myeloma cells primarily via caspase-independent AIF/Endo G pathway. Oncogene 24:5888–5896

    Article  PubMed  CAS  Google Scholar 

  13. Cande C, Vahsen N, Kouranti I, Schmitt E, Daugas E, Spahr C et al (2004) AIF and cyclophilin A cooperate in apoptosis-associated chromatinolysis. Oncogene 23:1514–1521

    Article  PubMed  CAS  Google Scholar 

  14. Zhu C, Wang X, Deinum J, Huang Z, Gao J, Modjtahedi N et al (2007) Cyclophilin A participates in the nuclear translocation of apoptosis-inducing factor in neurons after cerebral hypoxia-ischemia. J Exp Med 204:1741–1748

    Article  PubMed  CAS  Google Scholar 

  15. Krieser RJ, Eastman A (1998) The cloning and expression of human deoxyribonuclease II. a possible role in apoptosis. J Biol Chem 273:30909–30914

    Article  PubMed  CAS  Google Scholar 

  16. Torriglia A, Perani P, Brossas JY, Chaudun E, Treton J, Courtois Y et al (1998) l-DNase II, a molecule that links proteases and endonucleases in apoptosis, derives from the ubiquitous serpin leukocyte elastase inhibitor. Mol Cell Biol 18:3612–3619

    PubMed  CAS  Google Scholar 

  17. Law RH, Zhang Q, McGowan S, Buckle AM, Silverman GA, Wong W et al (2006) An overview of the serpin super family. Genome Biol 7:216

    Article  PubMed  Google Scholar 

  18. Silverman GA, Lomas DA (2004) Serpin identification, production, and characterization. Methods 32:71–72

    Article  PubMed  CAS  Google Scholar 

  19. Cooley J, Takayama TK, Shapiro SD, Schechter NM, Remold-O’Donnell E (2001) The serpin MNEI inhibits elastase-like and chymotrypsin-like serine proteases through efficient reactions at two active sites. Biochemistry 40:15762–15770

    Article  PubMed  CAS  Google Scholar 

  20. Padron-Barthe L, Courta J, Lepretre C, Nagbou A, Torriglia A (2008) Leukocyte elastase Inhibitor, the precursor of l-DNase II, inhibits apoptosis by interfering with caspase-8 activation. Biochim Biophys Acta 1783:1755–1766

    Article  PubMed  CAS  Google Scholar 

  21. Padron-Barthe L, Lepretre C, Martin E, Counis MF, Torriglia A (2007) Conformational modification of serpins transforms leukocyte elastase inhibitor into an endonuclease involved in apoptosis. Mol Cell Biol 27:4028–4036

    Article  PubMed  CAS  Google Scholar 

  22. Torriglia A, Chaudun E, Chany-Fournier F, Courtois Y, Counis MF (2001) Involvement of l-DNase II in nuclear degeneration during chick retina development. Exp Eye Res 72:443–453

    Article  PubMed  CAS  Google Scholar 

  23. Altairac S, Zeggai S, Perani P, Courtois Y, Torriglia A (2003) Apoptosis induced by Na+/H+antiport inhibition activates the LEI/l-DNase II pathway. Cell Death Differ 10:548–557

    Article  PubMed  CAS  Google Scholar 

  24. Belmokhtar CA, Torriglia A, Counis MF, Courtois Y, Jacquemin-Sablon A, Segal-Bendirdjian E (2000) Nuclear translocation of a leukocyte elastase inhibitor/elastase complex during staurosporine-induced apoptosis: role in the generation of nuclear l-DNase II activity. Exp Cell Res 254:99–109

    Article  PubMed  CAS  Google Scholar 

  25. Fombonne J, Padron L, Enjalbert A, Krantic S, Torriglia A (2006) A novel paraptosis pathway involving LEI/L-DNaseII for EGF-induced cell death in somato-lactotrope pituitary cells. Apoptosis 11:367–375

    Article  PubMed  CAS  Google Scholar 

  26. Gorrini C, Donzelli M, Torriglia A, Supino R, Brison O, Bernardi R et al (2003) Effect of apoptogenic stimuli on colon carcinoma cell lines with a different c-myc expression level. Int J Mol Med 11:737–742

    PubMed  CAS  Google Scholar 

  27. Huc L, Rissel M, Solhaug A, Tekpli X, Gorria M, Torriglia A et al (2006) Multiple apoptotic pathways induced by p53-dependent acidification in benzo[a]pyrene-exposed hepatic F258 cells. J Cell Physiol 208:527–537

    Article  PubMed  CAS  Google Scholar 

  28. Torriglia A, Negri C, Chaudun E, Prosperi E, Courtois Y, Counis MF et al (1999) Differential involvement of DNases in HeLa cell apoptosis induced by etoposide and long term-culture. Cell Death Differ 6:234–244

    Article  PubMed  CAS  Google Scholar 

  29. Bourges JL, Torriglia A, Valamanesh F, Benezra D, Renard G, Behar-Cohen FF (2007) Nitrosative stress and corneal transplant endothelial cell death during acute graft rejection. Transplantation 84:415–423

    Article  PubMed  Google Scholar 

  30. Bourges JL, Valamanesh F, Torriglia A, Jeanny JC, Savoldelli M, Renard G et al (2004) Cornea graft endothelial cells undergo apoptosis by way of an alternate (caspase-independent) pathway. Transplantation 78:316–323

    Article  PubMed  CAS  Google Scholar 

  31. Chahory S, Keller N, Martin E, Omri B, Crisanti P, Torriglia A (2010) Light induced retinal degeneration activates a caspase-independent pathway involving cathepsin D. Neurochem Int 57:278–287

    Article  PubMed  CAS  Google Scholar 

  32. Chahory S, Padron L, Courtois Y, Torriglia A (2004) The LEI/l-DNase II pathway is activated in light-induced retinal degeneration in rats. Neurosci Lett 367:205–209

    Article  PubMed  CAS  Google Scholar 

  33. Bottone MG, Soldani C, Tognon G, Gorrini C, Lazze MC, Brison O et al (2003) Multiple effects of paclitaxel are modulated by a high c-myc amplification level. Exp Cell Res 290:49–59

    Article  PubMed  CAS  Google Scholar 

  34. Altairac S, Wright SC, Courtois Y, Torriglia A (2003) l-DNase II activation by the 24 kDa apoptotic protease (AP24) in TNFalpha-induced apoptosis. Cell Death Differ 10:1109–1111

    Article  PubMed  CAS  Google Scholar 

  35. O’Connell AR, Holohan C, Torriglia A, Lee BW, Stenson-Cox C (2006) Characterization of a serine protease-mediated cell death program activated in human leukemia cells. Exp Cell Res 312:27–39

    Article  PubMed  Google Scholar 

  36. Lepretre C, Scovassi AI, Shah GM, Torriglia A (2009) Regulation of poly(ADP-ribose) polymerase-1 functions by leukocyte elastase inhibitor/LEI-derived DNase II during caspase-independent apoptosis. Int J Biochem Cell Biol 41:1046–1054

    Article  PubMed  CAS  Google Scholar 

  37. Lepretre C, Sidoli G, Scovassi AI, Torriglia A (2009) Leukocyte elastase inhibitor: a new regulator of PARP-1. Ann N Y Acad Sci 1171:25–31

    Article  PubMed  CAS  Google Scholar 

  38. Wang Y, Dawson VL, Dawson TM (2009) Poly(ADP-ribose) signals to mitochondrial AIF: a key event in parthanatos. Exp Neurol 218:193–202

    Article  PubMed  CAS  Google Scholar 

  39. Torriglia A, Chaudun E, Chany-Fournier F, Jeanny JC, Courtois Y, Counis MF (1995) Involvement of DNase II in nuclear degeneration during lens cell differentiation. J Biol Chem 270:28579–28585

    Article  PubMed  CAS  Google Scholar 

  40. Sahara S, Aoto M, Eguchi Y, Imamoto N, Yoneda Y, Tsujimoto Y (1999) Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation. Nature 401:168–173

    Article  PubMed  CAS  Google Scholar 

  41. Hangen E, Blomgren K, Benit P, Kroemer G, Modjtahedi N (2010) Life with or without AIF. Trends Biochem Sci 35:278–287

    Article  PubMed  CAS  Google Scholar 

  42. Baritaud M, Boujrad H, Lorenzo HK, Krantic S, Susin SA (2010) Histone H2AX: the missing link in AIF-mediated caspase-independent programmed necrosis. Cell Cycle 9:3166–3173

    Article  PubMed  CAS  Google Scholar 

  43. Liu KC, Huang YT, Wu PP, Ji BC, Yang JS, Yang JL et al (2011) The roles of AIF and Endo G in the apoptotic effects of benzyl isothiocyanate on DU 145 human prostate cancer cells via the mitochondrial signaling pathway. Int J Oncol 38:787–796

    PubMed  CAS  Google Scholar 

  44. Yuste VJ, Sanchez-Lopez I, Sole C, Moubarak RS, Bayascas JR, Dolcet X et al (2005) The contribution of apoptosis-inducing factor, caspase-activated DNase, and inhibitor of caspase-activated DNase to the nuclear phenotype and DNA degradation during apoptosis. J Biol Chem 280:35670–35683

    Article  PubMed  CAS  Google Scholar 

  45. Lin CC, Kuo CL, Lee MH, Lai KC, Lin JP, Yang JS et al (2011) Wogonin triggers apoptosis in human osteosarcoma U-2 OS cells through the endoplasmic reticulum stress, mitochondrial dysfunction and caspase-3-dependent signaling pathways. Int J Oncol 39:217–224

    PubMed  CAS  Google Scholar 

  46. Torriglia A, Lepretre C, Padron-Barthe L, Chahory S, Martin E (2008) Molecular mechanism of l-DNase II activation and function as a molecular switch in apoptosis. Biochem Pharmacol 76:1490–1502

    Article  PubMed  CAS  Google Scholar 

  47. Counis MF, Torriglia A (2000) DNases and apoptosis. Biochem Cell Biol 78:405–414

    Article  PubMed  CAS  Google Scholar 

  48. Counis MF, Torriglia A (2006) Acid DNases and their interest among apoptotic endonucleases. Biochimie 88:1851–1858

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

CL received a fellowship from Fondation pour la Recherche Médicale. INSERM and Retina France gave financial support to this work. All the AIF constructions were kindly provided by Dr. Santos Susin.

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Authors and Affiliations

  1. Centre de Recherches des Cordeliers, INSERM, UMR S 872, 15, rue de L’école de médecine, 75006, Paris, France

    Chloé Leprêtre, Guergana Tchakarska, Hounayda Blibech, Cécile Lebon & Alicia Torriglia

  2. Université Pierre et Marie Curie-Paris 6, Paris, France

    Chloé Leprêtre, Guergana Tchakarska, Hounayda Blibech, Cécile Lebon & Alicia Torriglia

  3. Universite Paris Descartes, Paris, France

    Chloé Leprêtre, Guergana Tchakarska, Hounayda Blibech, Cécile Lebon & Alicia Torriglia

  4. Université Paris Diderot-Paris 7, Paris, France

    Chloé Leprêtre & Guergana Tchakarska

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  1. Chloé Leprêtre
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  2. Guergana Tchakarska
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Correspondence to Alicia Torriglia.

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Leprêtre, C., Tchakarska, G., Blibech, H. et al. Apoptosis-inducing factor (AIF) and leukocyte elastase inhibitor/l-DNase II (LEI/LDNaseII), can interact to conduct caspase-independent cell death. Apoptosis 18, 1048–1059 (2013). https://doi.org/10.1007/s10495-013-0862-2

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