Apoptosis Control in Syncytia Induced by the HIV Type 1-Envelope Glycoprotein Complex: Role of Mitochondria and Caspases

doi:10.1084/jem.192.8.1081

Published online 9 October 2000.

This Article

	Full Text
	Full Text (PDF)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Ferri, K. F.
	Articles by Kroemer, G.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Ferri, K. F.
	Articles by Kroemer, G.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0022-1007/2000/10/1081/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 8, October 16, 2000 1081-1092

Original Article

Apoptosis Control in Syncytia Induced by the HIV Type 1–Envelope Glycoprotein Complex: Role of Mitochondria and Caspases

Karine F. Ferri^a, Etienne Jacotot^a, Julià Blanco^b, José A. Esté^b, Naoufal Zamzami^a, Santos A. Susin^a, Zhihua Xie^c, Greg Brothers^d, John C. Reed^c, Josef M. Penninger^d, and Guido Kroemer^a
^a Centre National de la Recherche Scientifique, UMR1599, Institut Gustave Roussy, F-94805 Villejuif, France
^b Institut de Recerca de la SIDA-Caixa, Laboratori de Retrovirologia, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Catalonia, Spain
^c The Burnham Institute, La Jolla, California 92037
^d The Amgen Institute and Ontario Cancer Institute, Department of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario M5G 2C1, Canada

Correspondence to: Guido Kroemer, CNRS-UMR1599, Institut Gustave Roussy, Pavillon de Recherche 1, 39 rue Camille-Desmoulins, F-94805 Villejuif, France. Tel:33-14-211-4235 Fax:33-14-211-5244

Syncytia arising from the fusion of cells expressing a lymphotropicHIV type 1–encoded envelope glycoprotein complex (Env)with cells expressing the CD4/CXC chemokine receptor 4 complexspontaneously undergo cell death. Here we show that this processis accompanied by caspase activation and signs of mitochondrialmembrane permeabilization (MMP), including the release of intermembraneproteins such as cytochrome c (Cyt-c) and apoptosis-inducingfactor (AIF) from mitochondria. In Env-induced syncytia, caspaseinhibition did not suppress AIF- and Cyt-c translocation, yetit prevented all signs of nuclear apoptosis. Translocation ofBax to mitochondria led to MMP, which was inhibited by microinjectedBcl-2 protein or bcl-2 transfection. Bcl-2 also prevented thesubsequent nuclear chromatin condensation and DNA fragmentation.The release of AIF occurred before that of Cyt-c and beforecaspase activation. Microinjection of AIF into syncytia sufficedto trigger rapid, caspase-independent Cyt-c release. Neutralizationof endogenous AIF by injection of an antibody prevented allsigns of spontaneous apoptosis occurring in syncytia, includingthe Cyt-c release and nuclear apoptosis. In contrast, Cyt-cneutralization only prevented nuclear apoptosis, and did notaffect AIF release. Our results establish that the followingmolecular sequence governs apoptosis of Env-induced syncytia:Bax-mediated/Bcl-2–inhibited MMP $->$ AIF release $->$ Cyt-c release $->$ caspase activation $->$ nuclear apoptosis.

Key Words: apoptosis-inducing factor, Bcl-2, cell death, cytochrome c,glycoprotein 120

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Gutierrez-Sanmartin, D., Varela-Ledo, E., Aguilera, A., Romero-Yuste, S., Romero-Jung, P., Gomez-Tato, A., Regueiro, B. J. (2008). Implication of p38 mitogen-activated protein kinase isoforms ({alpha}, {beta}, {gamma} and {delta}) in CD4+ T-cell infection with human immunodeficiency virus type I. J. Gen. Virol. 89: 1661-1671 [Abstract] [Full Text]
Edelstein, C. L. (2008). Mammalian Target of Rapamycin and Caspase Inhibitors in Polycystic Kidney Disease. CJASN 3: 1219-1226 [Abstract] [Full Text]
Bianchi, S. M., Prince, L. R., McPhillips, K., Allen, L., Marriott, H. M., Taylor, G. W., Hellewell, P. G., Sabroe, I., Dockrell, D. H., Henson, P. W., Whyte, M. K. B. (2008). Impairment of Apoptotic Cell Engulfment by Pyocyanin, a Toxic Metabolite of Pseudomonas aeruginosa. Am. J. Respir. Crit. Care Med. 177: 35-43 [Abstract] [Full Text]
Moin, S. M., Panteva, M., Jameel, S. (2007). The Hepatitis E Virus Orf3 Protein Protects Cells from Mitochondrial Depolarization and Death. J. Biol. Chem. 282: 21124-21133 [Abstract] [Full Text]
Srivastava, S., Banerjee, H., Chaudhry, A., Khare, A., Sarin, A., George, A., Bal, V., Durdik, J. M., Rath, S. (2007). Apoptosis-Inducing Factor Regulates Death in Peripheral T Cells. J. Immunol. 179: 797-803 [Abstract] [Full Text]
Hussain, A. R., Al-Jomah, N. A., Siraj, A. K., Manogaran, P., Al-Hussein, K., Abubaker, J., Platanias, L. C., Al-Kuraya, K. S., Uddin, S. (2007). Sanguinarine-Dependent Induction of Apoptosis in Primary Effusion Lymphoma Cells. Cancer Res. 67: 3888-3897 [Abstract] [Full Text]
Pauls, E., Senserrich, J., Clotet, B., Este, J. A. (2006). Inhibition of HIV-1 replication by RNA interference of p53 expression. J. Leukoc. Biol. 80: 659-667 [Abstract] [Full Text]
Huerta, L., Gomez-Icazbalceta, G., Soto-Ramirez, L., Viveros-Rogel, M., Rodriguez, R., Fuentes, L., Lamoyi, E., Larralde, C. (2005). Human immunodeficiency virus 1 (HIV-1) envelope-dependent cell-cell fusion modulation by HIV-positive sera is related to disease progression. J. Gen. Virol. 86: 1961-1966 [Abstract] [Full Text]
Salsman, J., Top, D., Boutilier, J., Duncan, R. (2005). Extensive Syncytium Formation Mediated by the Reovirus FAST Proteins Triggers Apoptosis-Induced Membrane Instability. J. Virol. 79: 8090-8100 [Abstract] [Full Text]
Park, M.-T., Kim, M.-J., Kang, Y.-H., Choi, S.-Y., Lee, J.-H., Choi, J.-A, Kang, C.-M., Cho, C.-K., Kang, S., Bae, S., Lee, Y.-S., Chung, H. Y., Lee, S.-J. (2005). Phytosphingosine in combination with ionizing radiation enhances apoptotic cell death in radiation-resistant cancer cells through ROS-dependent and -independent AIF release. Blood 105: 1724-1733 [Abstract] [Full Text]
Boya, P., Gonzalez-Polo, R.-A., Casares, N., Perfettini, J.-L., Dessen, P., Larochette, N., Metivier, D., Meley, D., Souquere, S., Yoshimori, T., Pierron, G., Codogno, P., Kroemer, G. (2005). Inhibition of Macroautophagy Triggers Apoptosis. Mol. Cell. Biol. 25: 1025-1040 [Abstract] [Full Text]
Perfettini, J.-L., Castedo, M., Nardacci, R., Ciccosanti, F., Boya, P., Roumier, T., Larochette, N., Piacentini, M., Kroemer, G. (2005). Essential role of p53 phosphorylation by p38 MAPK in apoptosis induction by the HIV-1 envelope. J. Exp. Med. 201: 279-289 [Abstract] [Full Text]
Andreau, K., Castedo, M., Perfettini, J.-L., Roumier, T., Pichart, E., Souquere, S., Vivet, S., Larochette, N., Kroemer, G. (2004). Preapoptotic Chromatin Condensation Upstream of the Mitochondrial Checkpoint. J. Biol. Chem. 279: 55937-55945 [Abstract] [Full Text]
Park, S.-J., Wu, C.-H., Gordon, J. D., Zhong, X., Emami, A., Safa, A. R. (2004). Taxol Induces Caspase-10-dependent Apoptosis. J. Biol. Chem. 279: 51057-51067 [Abstract] [Full Text]
Clarke, P., Meintzer, S. M., Wang, Y., Moffitt, L. A., Richardson-Burns, S. M., Johnson, G. L., Tyler, K. L. (2004). JNK Regulates the Release of Proapoptotic Mitochondrial Factors in Reovirus-Infected Cells. J. Virol. 78: 13132-13138 [Abstract] [Full Text]
Andreau, K., Perfettini, J.-L., Castedo, M., Metivier, D., Scott, V., Pierron, G., Kroemer, G. (2004). Contagious apoptosis facilitated by the HIV-1 envelope: fusion-induced cell-to-cell transmission of a lethal signal. J. Cell Sci. 117: 5643-5653 [Abstract] [Full Text]
Mele, R., Gomez Morales, M. A., Tosini, F., Pozio, E. (2004). Cryptosporidium parvum at Different Developmental Stages Modulates Host Cell Apoptosis In Vitro. Infect. Immun. 72: 6061-6067 [Abstract] [Full Text]
Blanco, J., Barretina, J., Clotet, B., Este, J. A. (2004). R5 HIV gp120-mediated cellular contacts induce the death of single CCR5-expressing CD4 T cells by a gp41-dependent mechanism. J. Leukoc. Biol. 76: 804-811 [Abstract] [Full Text]
Besse, B., Cande, C., Spano, J.-P., Martin, A., Khayat, D., Le Chevalier, T., Tursz, T., Sabatier, L., Soria, J.-C., Kroemer, G. (2004). Nuclear Localization of Apoptosis Protease Activating Factor-1 Predicts Survival after Tumor Resection in Early-Stage Non-Small Cell Lung Cancer. Clin. Cancer Res. 10: 5665-5669 [Abstract] [Full Text]
Perfettini, J.-L., Roumier, T., Castedo, M., Larochette, N., Boya, P., Raynal, B., Lazar, V., Ciccosanti, F., Nardacci, R., Penninger, J., Piacentini, M., Kroemer, G. (2004). NF-{kappa}B and p53 Are the Dominant Apoptosis-inducing Transcription Factors Elicited by the HIV-1 Envelope. J. Exp. Med. 199: 629-640 [Abstract] [Full Text]
Tirado, O. M., Mateo-Lozano, S., Sanders, S., Dettin, L. E., Notario, V. (2003). The PCPH Oncoprotein Antagonizes the Proapoptotic Role of the Mammalian Target of Rapamycin in the Response of Normal Fibroblasts to Ionizing Radiation. Cancer Res. 63: 6290-6298 [Abstract] [Full Text]
Boya, P., Andreau, K., Poncet, D., Zamzami, N., Perfettini, J.-L., Metivier, D., Ojcius, D. M., Jaattela, M., Kroemer, G. (2003). Lysosomal Membrane Permeabilization Induces Cell Death in a Mitochondrion-dependent Fashion. J. Exp. Med. 197: 1323-1334 [Abstract] [Full Text]
Cande, C., Cecconi, F., Dessen, P., Kroemer, G. (2003). Apoptosis-inducing factor (AIF): key to the conserved caspase-independent pathways of cell death?. J. Cell Sci. 115: 4727-4734 [Abstract] [Full Text]
Kominsky, D. J., Bickel, R. J., Tyler, K. L. (2002). Reovirus-Induced Apoptosis Requires Mitochondrial Release of Smac/DIABLO and Involves Reduction of Cellular Inhibitor of Apoptosis Protein Levels. J. Virol. 76: 11414-11424 [Abstract] [Full Text]
Yu, S.-W., Wang, H., Poitras, M. F., Coombs, C., Bowers, W. J., Federoff, H. J., Poirier, G. G., Dawson, T. M., Dawson, V. L. (2002). Mediation of Poly(ADP-Ribose) Polymerase-1-Dependent Cell Death by Apoptosis-Inducing Factor. Science 297: 259-263 [Abstract] [Full Text]
Castedo, M., Ferri, K. F., Blanco, J., Roumier, T., Larochette, N., Barretina, J., Amendola, A., Nardacci, R., Metivier, D., Este, J. A., Piacentini, M., Kroemer, G. (2001). Human Immunodeficiency Virus 1 Envelope Glycoprotein Complex-induced Apoptosis Involves Mammalian Target of Rapamycin/FKBP12-Rapamycin-associated Protein-mediated p53 Phosphorylation. J. Exp. Med. 194: 1097-1110 [Abstract] [Full Text]
Roggero, R., Robert-Hebmann, V., Harrington, S., Roland, J., Vergne, L., Jaleco, S., Devaux, C., Biard-Piechaczyk, M. (2001). Binding of Human Immunodeficiency Virus Type 1 gp120 to CXCR4 Induces Mitochondrial Transmembrane Depolarization and Cytochrome c-Mediated Apoptosis Independently of Fas Signaling. J. Virol. 75: 7637-7650 [Abstract] [Full Text]
Jacotot, E., Ferri, K. F., El Hamel, C., Brenner, C., Druillennec, S., Hoebeke, J., Rustin, P., Metivier, D., Lenoir, C., Geuskens, M., Vieira, H. L.A., Loeffler, M., Belzacq, A.-S., Briand, J.-P., Zamzami, N., Edelman, L., Xie, Z. H., Reed, J. C., Roques, B. P., Kroemer, G. (2001). Control of Mitochondrial Membrane Permeabilization by Adenine Nucleotide Translocator Interacting with HIV-1 Viral Protein R and Bcl-2. J. Exp. Med. 193: 509-520 [Abstract] [Full Text]
Miramar, M. D., Costantini, P., Ravagnan, L., Saraiva, L. M., Haouzi, D., Brothers, G., Penninger, J. M., Peleato, M. L., Kroemer, G., Susin, S. A. (2001). NADH Oxidase Activity of Mitochondrial Apoptosis-inducing Factor. J. Biol. Chem. 276: 16391-16398 [Abstract] [Full Text]
Petit, F., Arnoult, D., Lelievre, J.-D., Parseval, L. M.-d., Hance, A. J., Schneider, P., Corbeil, J., Ameisen, J. C., Estaquier, J. (2002). Productive HIV-1 Infection of Primary CD4+ T Cells Induces Mitochondrial Membrane Permeabilization Leading to a Caspase-independent Cell Death. J. Biol. Chem. 277: 1477-1487 [Abstract] [Full Text]