The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore

Journal of Experimental Medicine

Volumn 191, Issue 1, 2000, Pages 33-45

  Jacotot, Etienne ^a   Ravagnan, Luigi ^a   Loeffler, Markus ^a   Ferri, Karine F ^a   Vieira, Helena L A ^a   Zamzami, Naoufal ^a   Costantini, Paola ^a   Druillennec, Sabine ^b   Hoebeke, Johan ^a   Briand, Jean Paul ^a   Irinopoulou, Theano ^c   Daugas, Eric ^a   Susin, Santos A ^a   Cointe, Denis ^d   Xie, Zhi Hua ^e   Reed, John C ^e   Roques, Bernard P ^b   Kroemer, Guido ^a,f  

^a CNRS   (France)

^b INSERM   (France)

^c HÔPITAL BROUSSAIS   (France)

^d HÔPITAL ANTOINE BÉCLÈRE   (France)

^e BURNHAM INSTITUTE   (United States)

^f Burnham Institute ^*  (France)

Author keywords

Apoptosis; Bcl 2; Cell death; Mitochondria; Vpr

Indexed keywords

ADENINE NUCLEOTIDE TRANSLOCASE; ANION CHANNEL; CYTOCHROME C OXIDASE; PROTEIN BAX; PROTEIN BCL 2; VPR PROTEIN;

ANIMAL CELL; APOPTOSIS; ARTICLE; CELL KILLING; CELL STRAIN COS1; CHANNEL GATING; CONTROLLED STUDY; CYTOTOXICITY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; LEUKEMIA CELL LINE; MEMBRANE PERMEABILITY; MEMBRANE POTENTIAL; MITOCHONDRIAL MEMBRANE; MOUSE; NONHUMAN; PRIORITY JOURNAL;

APOPTOSIS; CELL-FREE SYSTEM; GENE PRODUCTS, VPR; HIV-1; HUMANS; JURKAT CELLS; MITOCHONDRIA; PERMEABILITY; PROTO-ONCOGENE PROTEINS C-BCL-2;

EID: 0034598337     PISSN: 00221007     EISSN: None     Source Type: Journal    
DOI: 10.1084/jem.191.1.33     Document Type: Article

References (68)

1. Levy, J.A. 1993. Pathogenesis of HIV infection. Microbiol. Rev. 57:222-230.
2. Fauci, A.S. 1996. Host factors and the pathogenesis of HIVinduced disease, Nature. 384:529-534.
3. Emerman, M., and M.H. Malim. 1998. HIV-1 regulatory/ accessory genes: keys to unraveling viral and host cell biology. Science. 280: 1880-1884.
4. Hellerstein, M., M.B. Hanley, D. Cesar, C. Papageorgopoulos, E. Wieder, D. Schmidt, R. Hoh, R. Neese, D. Macallan, S. Deeks, et al. 1999. Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans. Nat. Med. 5:83-89.
5. Cullen, B.R. 1998. HIV-1 auxiliary proteins: making connections in a dying cell. Cell. 93:685-692.
6. Levy, D.N., Y. Refaeli, B.R. MacGregor, and D.B. Weiner. 1994. Serum Vpr regulates productive infection and latency of human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. USA. 91:10873-10877.
7. Goh, W.C., M.E. Rogel, C.M. Kinsey, S.F. Michale, P.N. Fultz, M.A. Nowak, B.H. Hahn, and M. Emerman. 1998. HIV-1 Vpr increases viral expression by manipulation of the cell cycle: a mechanism for selection of Vpr in vivo. Nat. Med. 4:65-71.
8. Yao, X.J., A.J. Mouland, R.A. Subbramanian, J. Forget, N. Rougeau, D. Bergeron, and E.A. Cohen. 1998. Vpr stimulates viral expression and induces cell killing in human immunodeficiency virus type 1-infected dividing Jurkat T cells. J. Virol. 72:4686-4693.
9. Stewart, S.A., B. Poon, J.B.M. Jowett, and I.S.Y. Chen. 1997. Human immunodeficiency virus type 1 vpr induces apoptosis following cell cycle arrest. J. Virol. 71:5579-5592.
10. Piller, S.C., P. Jans, P.W. Gage, and D.A. Jans. 1998. Extracellular HIV-1 virus protein R causes a large inward current and cell death in cultured hippocampal neurons: implications for AIDS pathology. Proc. Natl. Acad. Sci. USA. 95:4595-4600.
11. Ayyavoo, V., A. Mahboubi, S. Mahalingam, R. Romalingam, S. Kudchodkar, W.V. Williams, D.R. Green, and D.B. Weiner. 1997. HIV-1 Vpr suppresses immune activation and apoptosis through regulation of nuclear factor kappa B. Nat. Med. 10:1117-1123.
12. Lazebnik, Y.A., S. Cole, C.A. Cooke, W.G. Nelson, and W.C. Earnshaw. 1993. Nuclear events of apoptosis in vitro in cell-tree mitotic extracts: a model system for analysis of the active phase ot apoptosis. J. Cell Biol. 123:7-22.
13. Zamzami, N., S.A. Susin, P. Marchetti, T. Hirsch, I. Gómez-Monterrey, M. Castedo, and G. Kroemer. 1996. Mitochondrial control of nuclear apoptosis. J. Exp. Med. 183:1533-1544.
14. Liu, X.S., C.N. Kim, J. Yang, R. Jemmerson, and X. Wang. 1996. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome C. Cell. 86:147-157.
15. Susin, S.A., N. Zamzami, M. Castedo, T. Hirsch, P. Marchetti, A. Macho, E. Daugas, M. Geuskens, and G. Kroemer. 1996. Bcl-2 inhibits the mitochondrial release of an apoptogenic protease. J. Exp. Med. 184:1331-1342.
16. Ellerby, H.M., S.J. Martin, L.M. Ellerby, S.S. Naiem, S. Kabizadeh, G.S. Salvesen, C.A. Casiano, N.R. Cashman, D.R. Green, and D.E. Bredesen. 1997. Establishment of a cell-tree system of neuronal apoptosis: comparison of premitochondrial, mitochondrial, and postmitochondrial phases. J. Neurosci. 17:6165-6178.
17. Kluck, R.M., E. Bossy-Wetzel, D.R. Green, and D.D. Newmeyer. 1997. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science. 275:1132-1136.
18. Susin, S.A., H.K. Lorenzo, N. Zamzami, I. Marzo, N. Larochette, P.M. Alzari, and G. Kroemer. 1999. Mitochondrial release of caspases-2 and -9 during the apoptotic process. J. Exp. Med. 189:381-394.
19. Susin, S.A., H.K. Lorenzo, N. Zamzami, I. Marzo, B.E. Snow, G.M. Brothers, J. Mangion, E. Jacotot, P. Costantini, M. Loeffler, et al. 1999. Molecular characterization of mitochondrial apoptosis-inducing factor (AIF). nature. 397:441-446.
20. Liu, X.S., P. Li, P. Widlack, H. Zou, X. Luo, W.T. Garrard, and X.D. Wang. 1998. The 40-kDa subunit of DNA fragmentation factor induces DNA fragmentation and chromatin condensation during apoptosis. Proc. Natl. Acad. Sci. USA. 95:8461-8466.
21. Enari, M., H. Sakahira, H. Yokoyoma, K. Okawa, A. Iwamtsu, and S. Nagata. 1998. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor [CAD. Nature. 391:43-50.
22. Samali, A., J. Cai, B. Zhivotovsky, D.P. Jones, and S. Orrenius. 1999. Presence of a pre-apoptotic complex of procaspase-3, hsp60, and hsp10 in the mitochondrial fraction of Jurkat cells. EMBO (Eur. Mol. Biol. Organ.) J. 18:2040-2048.
23. Xanthoudakis, S., S. Roy, D. Rasper, T. Hennessey, Y. Aubin, R. Cassady, P. Tawa, R. Ruel, A. Rosen, and D.W. Nicholson. 1999. Hsp60 accelerates the maturation of procaspase-3 by upstream activator proteases during apoptosis. EMBO (Eur. Mol. Biol. Organ.) J. 18:2049-2056.
24. Cosulich, S.C., V. Worrall, P.J. Hege, S. Green, and P.R. Clarke. 1997. Regulation of apoptosis by BH3 domains in a cell-free system. Curr. Biol. 12:913-920.
25. Jürgensmeier, J.M., Z. Xie, Q. Deveraux, L. Ellerby, D. Bredesen, and J.C. Reed. 1998. Bax directly induces release of cytochrome c from isolated mitochondria. Proc. Natl. Acad. Sci. USA. 95:4997-5002.
26. Luo, X., I. Budiharjo, H. Zou, C. Slaughter, and X. Wang. 1998. Bid, a Bcl-2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell. 94:481-490.
27. Marzo, I., C. Brenner, N. Zamzami, J. Jürgensmeier, S.A. Susin, H.L.A. Vieira, M.-C. Prévost, Z. Xie, S. Matsuyama, J.C. Reed, et al. 1998. Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis. Science. 281:2027-2031.
28. Narita, M., S. Shimizu, T. Ito, T. Chittenden, R.J. Lutz, H. Matsuda, and Y. Tsujimoto. 1998. Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc. Natl. Acad. Sci. USA. 95:14681-14686.
29. Marzo, I., C. Brenner, N. Zamzami, S.A. Susin, G. Beutner, D. Brdiczka, R. Rémy, Z.-H. Xie, J.C. Reed, and G. Kroemer. 1998. The permeability transition pore complex: a target for apoptosis regulation by caspases and Bcl-2 related proteins. J. Exp. Med. 187:1261-1271.
30. Crompton, M., S. Virji, and J.M. Ward. 1998. Cyclophilin-C hinds strongly to complexes of the voltage-dependent anion channel and the adenine nucleotide translocase to form the permeability transition pore. Eur. J. Biochem. 258:729-735.
31. Ravagnan, L., I. Marzo, P. Costantini, S.A. Susin, N. Zamzami, P.X. Petit, F. Hirsch, M.-F. Poupon, L. Miccoli, Z. Xie, et al. 1999. Lonidamine triggers apoptosis via a direct, Bcl-2-inhibited effect on the mitochondrial permeability transition pore. Oncogene: 18:2537-2546.
32. Fulda, S., C. Scaffidi, S.A. Susin, P.H. Krammer, G. Kroenier, M.E. Peter, and K.M. Debatin. 1998. Activation of mitochondria and release of mitochondrial apoptogenic factors by betulinic acid. J. Biol. Chem. 273:33942-33948.
33. Larochette, N., D. Decaudin, E. Jacotot, C. Brenner, I. Marzo, S.A. Susin, N. Zamzami, Z. Xie, J.C. Reed, and G. Kroemer. 1999. Arsenite induces apoptosis via a direct effect on the mitochondrial permeability transition pore. Exp. Cell Res. 249:413-421.
34. Zamzami, N., I. Marzo, S.A. Susin, C. Brenner, N. Larochette, P. Marchetti, J. Reed, R. Kofler, and G. Kroemer. 1998. The thiol-crosslinking agent diamide overcomes the upoptosis-inhibitory effect of Bcl-2 by enforcing mitochondrial permeability transition. Oncogene. 16:1055-1063.
35. Trost, L.C., and J.J. Lemasters. 1996. The mitochondrial permeability transition: a new pathophysiological mechanism for Reye's syndrome and toxic liver injury. J. Pharmacol. Exp. Ther. 278:1000-1005.
36. Costantini, P., B.V. Chernyak, V. Petronilli, and P. Bernardi. 1996. Modulation of the mitochondrial permeability transition pore by pyridine nucleotides and dithiol oxidation at two separate sites. J. Biol. Chem. 271:6746-6751.
37. Susin, S.A., N. Zamzami, M. Castedo, E. Daugas, H.-G. Wang, S. Geley, F. Fassy, J. Reed, and G. Kroemer. 1997. The central executioner of apoptosis. Multiple links between protease activation and mitochondria in Fas/Apo-1/CD95- and ceramide-induced apoptosis. J. Exp. Med. 186:25-37.
38. Kroemer, G., B. Dallaporta, and M. Resche-Rigon. 1998. The mitochondrial death/life regulator in apoptosis and necrosis. Annu. Rev. Pghysiol. 60:619-642.
39. De Rocquigny, H., P. Petit-Jean, V. Tanchou, D. Decimo, L. Drouot, T. Delaunay, J.L. Darlix, and B.P. Roques. 1997. The zinc fingers of HIV nucleocapsid protein NCp7 direct interactions with the viral regulatory protein Vpr. J. Biol. Chem. 272:30753-30759.
40. Schüler, W., K. Wecker, H. de Rocquigny, Y. Baudat, J. Sire, and B.P. Roques. 1999. NMR structure of the (52-96) C-terminal domain of the HIV-1 regulatory protein Vpr: molecular insights into its biological functions. J. Mol. Biol. 285:2105-2117.
41. + T-or monocytic cell lines J. Virol. 72:9698-9705.
42. Zamzami, N., P. Marchetti, M. Castedo, D. Decaudin, A. Macho, T. Hirsch, S.A. Susin, P.X. Petit, B. Mignotte, and G. Kroemer. 1995. Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death. J. Exp. Med. 182: 367-377.
43. Nicoletti, I., G. Migliorati, M.C. Pagliacci, and C. Riccardi. 1991. A rapid simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J. Immunol. Methods. 139:271-280.
44. Shimizu, S., Y. Eguchi, W. Kamiike, Y. Funahashi, A. Mignon, V. Lacronique, H. Matsuda, and Y. Tsujimoto. 1998. Bcl-2 prevents apoptotic mitochondrial dysfunction by regulating proton flux. Proc. Natl. Acad. Sci. USA. 95:1455-1459.
45. 2+/tert-butylhydroperoxide treated mitochondria. Biochemistry. 35:15440-15446.
46. Blachly-Dyson, E., J.M. Song, W.J. Wolgang, M. Colombini, and M. Forte. 1997. Multicopy suppressors of phenotypes resulting from the absence of yeast VDAC encode a VDAC-like protein. Mol. Cell. Biol. 17:5727-5738.
47. Blachly-Dyson, E., E.B. Zambronicz. W.H. Yu, V. Adams, E.R. McCabe, J. Adelman, M. Colombini, and M. Forte. 1993. Cloning and functional expression in yeast of two human isoforms of the outer mitochondrial membrane channel, the voltage dependent anion channel. J. Biol. Chem. 268: 1835-1841.
48. Drgon, T., L. Sabova, N. Nelson, and J. Kolarov. 1991. ADP/ATP translocator is essential for anaerobic growth of yeast Saccharomyces cerevisiae. FEBS Lett. 289:159-162.
49. Nelson, D.R., J.E. Lawson, M. Klingenberg, and M.G. Douglas. 1993. Site-directed mutagenesis of the yeast mitochondrial ADP/ATP translocator-6 arginines and one lysine are essential. J. Mol. Biol. 230:1159-1170.
50. Macreadie, I.G., C.K. Arunagiri, D.R. Hewish, J.F. White, and A.A. Azad. 1996. Extracellular addition of a domain of HIV-1 Vpr containing the amino acid sequence motif H(S/ F)RIG causes cell membrane permeabilization and death. Mol. Microbiol. 19:1185-1192.
51. Thorsness, P.E., K.H. White, and T.D. Fox. 1993. Inactivation of YME1, a member of the fts H-SEC18-PAZ1-CDC48 family of putative ATPase-encoding genes, causes increased escape of DNA from mitochondria in Saccharomyces cerevisiae. Mol. Cell. Biol. 13:5418-5426.
52. Macreadie, I.G., L.A. Castelli, D.R. Hewish, A. Kirkpatrick, A.C. Ward, and A.A. Azad. 1995. A domain of human immunodeficiency virus type 1 Vpr containing repeated H(S/ F)RIG amino acid motifs causes cell growth arrest and structural defects. Proc. Natl. Acad. Sci. USA. 92:2770-2774.
53. Zhang, S., D. Pointer, G. Singer, Y. Feng, K. Park, and L.-J. Zhao. 1998. Direct binding to nucleic acids by Vpr of human immunodeficiency virus type 1. Gene. 212:157-166.
54. Piller, S.C., G.D. Ewart, D.A. Jans, P.W. Gage, and G.B. Cox. 1999. The amino-terminal region of Vpr from human immunodeficiency virus type 1 forms ion channels and kills neurons. J. Virol. 73:4230-4238.
55. Macreadie, I.G., D.R. Thorburn, D.M. Kirby, L.A. Castelli, N.L. Derozario, and A.A. Azad. 1997. HIV-1 protein Vpr causes gross mitochondrial dysfunction in the yeast Saccharomyces cerevisiae. FEBS Lett. 410:145-149.
56. Mancini, M., D.W. Nicholson, S. Roy, N.A. Thornberry, E.P. Peterson, L.A. Casciola-Rosen, and A. Rosen. 1998. The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling. J. Cell Biol. 140:1485-1495.
57. Lu, Y.L., P. Spearman, and L. Ratner. 1993. Human immunodeficiency virus type 1 viral protein R localization in intact cells and virions. J. Virol. 67:6542-6550.
58. Zhou, Y., Y. Lu, and L. Ratner. 1998. Arginine residues in the C-terminus of HIV-1 Vpr are important for nuclear localization and cell cycle arrest. Virology. 242:414-424.
59. Westendorp, M.O., V.A. Shatrov, K. Schulze-Osthoff, R. Frank, M. Kraft, M. Los, P.H. Krammer, W. Dröge, and V. Lehrmann. 1995. HIV-1 Tat potentiates TNF-induced NF-κB activation and cytotoxicity by altering the cellular redox state. EMBO (Eur. Mol. Biol. Organ.) J. 14:546-554.
60. Strack, P.R., M.W. Frey, C.J. Rizzo, B. Cordova, H.J. George, R. Meade, S.W. Jo, J. Corman, R. Tritch, and B.D. Korant. 1996. Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2. Proc. Natl. Acad. Sci. USA. 93:9571-9576.
61. Macho, A., M. Castedo, P. Marchetti, J.J. Aguilar, D. Decaudin, N. Zanizami, P.M. Girard, J. Uriel, and G. Kroemer. 1995. Mitochondrial dysfunctions in circulating T lymphocytes from human immunodeficiency virus-1 carriers. Blood. 86:2481-2487.
62. Carbonari, M., M. Pesce, M. Cibati, A. Modica, L. Dellanna, G. Doffizi, A. Angelici, S. Uccini, A. Modesti, and M. Fiorilli. 1997. Death of bystander cells by a novel pathway involving early mitochondrial damage in human immunodeficiency virus-related lymphadenopathy. Blood. 90:209-216.
63. Frankel, A.D., and J.A.T. Young. 1998. HIV-1: fifteen proteins and an RNA. Annu. Rev. Biochem. 67:1-25.
64. Heimech, M., X.-J. Yas, F. Bachand, N. Rougeau, and E.A. Cohen. 1999. Human immunodeficiency virus type 1 (HIV-1) Vpr functions as an immediate-early protein during HIV-1 infection. J. Virol. 73:4101-4109.
65. Tschopp, J., M. Thome, K. Hofmann, and E. Meinl. 1998. The fight of viruses against apoptosis. Curr. Opin. Genet. Dev. 8:82-87.
66. Evans, E.K., T. Kuwana, S.L. Strum, J.J. Smith, D.D. Newmeyer, and S. Kornbluth. 1997. Reaper-induced apoptosis in a vertebrate system. EMBO (Eur. Mol. Biol. Organ.) J. 16: 7272-7381.
67. Claveria, C., J.P. Albar, A. Serrano, J.M. Buesa, J.M. Barbero, A.C. Martinez, and M. Torres. 1998. Drosophila grim induces apoptosis in mammalian cells. EMBO (Eur. Mol. Biol. Organ.) J. 17:7199-7208.
68. Haining, W.N., C. Carboy-Newcomb, C.L. Wei. and H. Steller. 1999. The proapoptotic function of Drosophila Hid is conserved in mammalian cells. Proc. Natl. Acad. Sci. USA. 96: 4936-4941.