Guido Kroemer

Critical involvement of the ATM-dependent DNA damage response in the apoptotic demise of HIV-1-elicited syncytia. (2008)

Perfettini, Jean-Luc, Nardacci, Roberta, Bourouba, Mehdi, Subra, Frédéric, Gros, Laurent, Séror, Claire, ...

DNA damage can activate the oncosuppressor protein ataxia telangiectasia mutated (ATM), which phosphorylates the histone H2AX within characteristic DNA damage foci. Here, we show that ATM undergoes...

Critical involvement of the ATM-dependent DNA damage response in the apoptotic demise of HIV-1-elicited syncytia. (2008)

Perfettini, Jean-Luc, Nardacci, Roberta, Bourouba, Mehdi, Subra, Frédéric, Gros, Laurent, Séror, Claire, ...

DNA damage can activate the oncosuppressor protein ataxia telangiectasia mutated (ATM), which phosphorylates the histone H2AX within characteristic DNA damage foci. Here, we show that ATM undergoes...

An AIF orthologue regulates apoptosis in yeast (2004)

Wissing, Silke, Ludovico, Paula, Herker, Eva, Buttner, Sabrina, Engelhardt, Silvia, Decker, Thorsten, ...

Apoptosis-inducing factor (AIF), a key regulator of cell death, is essential for normal mammalian development and participates in pathological apoptosis. The proapoptotic nature of AIF and its mode...

NEW EMBO MEMBER’S REVIEW: Viral and bacterial proteins regulating apoptosis at the mitochondrial level

Boya, Patricia, Roques, Bernard, Kroemer, Guido

Mitochondrial membrane permeabilization (MMP) is a critical step of several apoptotic pathways. Some infectious intracellular pathogens can regulate (induce or inhibit) apoptosis of their host cells...

Sequential involvement of Cdk1, mTOR and p53 in apoptosis induced by the HIV-1 envelope

Castedo, Maria, Roumier, Thomas, Blanco, Julià, Ferri, Karine F., Barretina, Jordi, Tintignac, Lionel A., ...

Syncytia arising from the fusion of cells expressing the HIV-1-encoded Env gene with cells expressing the CD4/CXCR4 complex undergo apoptosis following the nuclear translocation of mammalian target...

Mutant MyoD Lacking Cdc2 Phosphorylation Sites Delays M-Phase Entry

Tintignac, Lionel A. J., Sirri, Valentina, Leibovitch, Marie Pierre, Lécluse, Yann, Castedo, Maria, Metivier, Didier, ...

The transcription factors MyoD and Myf-5 control myoblast identity and differentiation. MyoD and Myf-5 manifest opposite cell cycle-specific expression patterns. Here, we provide evidence that MyoD...

AIF deficiency compromises oxidative phosphorylation

Vahsen, Nicola, Candé, Céline, Brière, Jean-Jacques, Bénit, Paule, Joza, Nicholas, Larochette, Nathanael, ...

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that, after apoptosis induction, translocates to the nucleus where it participates in apoptotic chromatinolysis. Here, we show that...

Inhibition of Macroautophagy Triggers Apoptosis†

Boya, Patricia, González-Polo, Rosa-Ana, Casares, Noelia, Perfettini, Jean-Luc, Dessen, Philippe, Larochette, Nathanael, ...

Mammalian cells were observed to die under conditions in which nutrients were depleted and, simultaneously, macroautophagy was inhibited either genetically (by a small interfering RNA targeting Atg5,...

Dynamic changes in Mcl-1 expression regulate macrophage viability or commitment to apoptosis during bacterial clearance

Marriott, Helen M., Bingle, Colin D., Read, Robert C., Braley, Karen E., Kroemer, Guido, Hellewell, Paul G., ...

Macrophages are critical effectors of bacterial clearance and must retain viability, despite exposure to toxic bacterial products, until key antimicrobial functions are performed. Subsequently,...

Inhibition of adenine nucleotide translocator pore function and protection against apoptosis in vivo by an HIV protease inhibitor

Weaver, Joel G.R., Tarze, Agathe, Moffat, Tia C., LeBras, Morgane, Deniaud, Aurelien, Brenner, Catherine, ...

Inhibitors of HIV protease have been shown to have antiapoptotic effects in vitro, yet whether these effects are seen in vivo remains controversial. In this study, we have evaluated the impact of the...

Pharmacological manipulation of cell death: clinical applications in sight?

Green, Douglas R., Kroemer, Guido

This series of Reviews on cell death explores the creation of new therapies for correcting excessive or deficient cell death in human disease. Signal transduction pathways controlling cell death and...

Muscle-Specific Loss of Apoptosis-Inducing Factor Leads to Mitochondrial Dysfunction, Skeletal Muscle Atrophy, and Dilated Cardiomyopathy

Joza, Nicholas, Oudit, Gavin Y., Brown, Doris, Bénit, Paule, Kassiri, Zamaneh, Vahsen, Nicola, ...

Cardiac and skeletal muscle critically depend on mitochondrial energy metabolism for their normal function. Recently, we showed that apoptosis-inducing factor (AIF), a mitochondrial protein...

NEW EMBO MEMBER’S REVIEW: Viral and bacterial proteins regulating apoptosis at the mitochondrial level

Boya, Patricia, Roques, Bernard, Kroemer, Guido

Mitochondrial membrane permeabilization (MMP) is a critical step of several apoptotic pathways. Some infectious intracellular pathogens can regulate (induce or inhibit) apoptosis of their host cells...

Sequential involvement of Cdk1, mTOR and p53 in apoptosis induced by the HIV-1 envelope

Castedo, Maria, Roumier, Thomas, Blanco, Julià, Ferri, Karine F., Barretina, Jordi, Tintignac, Lionel A., ...

Syncytia arising from the fusion of cells expressing the HIV-1-encoded Env gene with cells expressing the CD4/CXCR4 complex undergo apoptosis following the nuclear translocation of mammalian target...

Mutant MyoD Lacking Cdc2 Phosphorylation Sites Delays M-Phase Entry

Tintignac, Lionel A. J., Sirri, Valentina, Leibovitch, Marie Pierre, Lécluse, Yann, Castedo, Maria, Metivier, Didier, ...

The transcription factors MyoD and Myf-5 control myoblast identity and differentiation. MyoD and Myf-5 manifest opposite cell cycle-specific expression patterns. Here, we provide evidence that MyoD...

AIF deficiency compromises oxidative phosphorylation

Vahsen, Nicola, Candé, Céline, Brière, Jean-Jacques, Bénit, Paule, Joza, Nicholas, Larochette, Nathanael, ...

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that, after apoptosis induction, translocates to the nucleus where it participates in apoptotic chromatinolysis. Here, we show that...

Inhibition of Macroautophagy Triggers Apoptosis†

Boya, Patricia, González-Polo, Rosa-Ana, Casares, Noelia, Perfettini, Jean-Luc, Dessen, Philippe, Larochette, Nathanael, ...

Mammalian cells were observed to die under conditions in which nutrients were depleted and, simultaneously, macroautophagy was inhibited either genetically (by a small interfering RNA targeting Atg5,...

Dynamic changes in Mcl-1 expression regulate macrophage viability or commitment to apoptosis during bacterial clearance

Marriott, Helen M., Bingle, Colin D., Read, Robert C., Braley, Karen E., Kroemer, Guido, Hellewell, Paul G., ...

Macrophages are critical effectors of bacterial clearance and must retain viability, despite exposure to toxic bacterial products, until key antimicrobial functions are performed. Subsequently,...

Inhibition of adenine nucleotide translocator pore function and protection against apoptosis in vivo by an HIV protease inhibitor

Weaver, Joel G.R., Tarze, Agathe, Moffat, Tia C., LeBras, Morgane, Deniaud, Aurelien, Brenner, Catherine, ...

Inhibitors of HIV protease have been shown to have antiapoptotic effects in vitro, yet whether these effects are seen in vivo remains controversial. In this study, we have evaluated the impact of the...

Pharmacological manipulation of cell death: clinical applications in sight?

Green, Douglas R., Kroemer, Guido

This series of Reviews on cell death explores the creation of new therapies for correcting excessive or deficient cell death in human disease. Signal transduction pathways controlling cell death and...

Muscle-Specific Loss of Apoptosis-Inducing Factor Leads to Mitochondrial Dysfunction, Skeletal Muscle Atrophy, and Dilated Cardiomyopathy

Joza, Nicholas, Oudit, Gavin Y., Brown, Doris, Bénit, Paule, Kassiri, Zamaneh, Vahsen, Nicola, ...

Cardiac and skeletal muscle critically depend on mitochondrial energy metabolism for their normal function. Recently, we showed that apoptosis-inducing factor (AIF), a mitochondrial protein...

Apoptosome-Independent Activation of the Lysosomal Cell Death Pathway by Caspase-9▿ †

Gyrd-Hansen, Mads, Farkas, Thomas, Fehrenbacher, Nicole, Bastholm, Lone, Høyer-Hansen, Maria, Elling, Folmer, ...

The apoptosome, a heptameric complex of Apaf-1, cytochrome c, and caspase-9, has been considered indispensable for the activation of caspase-9 during apoptosis. By using a large panel of genetically...

Characterization of Cell Death Pathways in Human Immunodeficiency Virus-Associated Encephalitis

Nardacci, Roberta, Antinori, Andrea, Larocca, Luigi Maria, Arena, Vincenzo, Amendola, Alessandra, Perfettini, Jean-Luc, ...

Human immunodeficiency virus (HIV)-associated dementia is a neurodegenerative syndrome characterized by cognitive decline, personality change, and motor deficits. HIV-associated encephalitis (HAE),...

Apoptosis regulation in tetraploid cancer cells

Castedo, Maria, Coquelle, Arnaud, Vivet, Sonia, Vitale, Ilio, Kauffmann, Audrey, Dessen, Philippe, ...

Tetraploidy can result in cancer-associated aneuploidy. As shown here, freshly generated tetraploid cells arising due to mitotic slippage or failed cytokinesis are prone to undergo Bax-dependent...

Mitochondrial Release of Apoptosis-Inducing Factor and Cytochrome c During Smooth Muscle Cell Apoptosis

Granville, David J., Cassidy, Brighid A., Ruehlmann, Dietrich O., Choy, Jonathan C., Brenner, Catherine, Kroemer, Guido, ...

Photodynamic therapy (PDT) is under investigation for the treatment of intimal hyperplastia in conditions such as atherosclerosis and restenosis. Although smooth muscle cells (SMCs) may be a key...

Clearance of Apoptotic Photoreceptors: Elimination of Apoptotic Debris into the Subretinal Space and Macrophage-Mediated Phagocytosis via Phosphatidylserine Receptor and Integrin αvβ3

Hisatomi, Toshio, Sakamoto, Taiji, Sonoda, Koh-hei, Tsutsumi, Chikako, Qiao, Hong, Enaida, Hiroshi, ...

The effective phagocytotic clearance of apoptotic debris is fundamental to the maintenance of neural tissues during apoptosis. Retinal photoreceptors undergo apoptosis after retinal detachment....

Relocalization of Apoptosis-Inducing Factor in Photoreceptor Apoptosis Induced by Retinal Detachment in Vivo

Hisatomi, Toshio, Sakamoto, Taiji, Murata, Toshinori, Yamanaka, Ichiro, Oshima, Yuji, Hata, Yasuaki, ...

Apoptosis-inducing factor (AIF) is a novel mediator in apoptosis. AIF is a flavoprotein that is normally confined to the mitochondrial intermembrane space, yet translocates to the nucleus in several...

Mitochondrial Cell Death Control in Familial Parkinson Disease

Kroemer, Guido, Blomgren, Klas

Many sporadic cases of Parkinsons disease have mutations in the PINK protein kinase, whose substrate is now revealed to be a protein that protects mitochondria from oxidative stress.

Cytopathic effects of the cytomegalovirus-encoded apoptosis inhibitory protein vMIA

Poncet, Delphine, Pauleau, Anne-Laure, Szabadkai, Gyorgy, Vozza, Angelo, Scholz, Sebastian R., Le Bras, Morgane, ...

Replication of human cytomegalovirus (CMV) requires the expression of the viral mitochondria–localized inhibitor of apoptosis (vMIA). vMIA inhibits apoptosis by recruiting Bax to mitochondria,...

Why yeast cells can undergo apoptosis: death in times of peace, love, and war

Büttner, Sabrina, Eisenberg, Tobias, Herker, Eva, Carmona-Gutierrez, Didac, Kroemer, Guido, Madeo, Frank

The purpose of apoptosis in multicellular organisms is obvious: single cells die for the benefit of the whole organism (for example, during tissue development or embryogenesis). Although apoptosis...

Molecular mechanisms of sulfasalazine-induced T-cell apoptosis

Liptay, Susanne, Fulda, Simone, Schanbacher, Marta, Bourteele, Soizic, Ferri, Karine F, Kroemer, Guido, ...

Impaired apoptosis of T-lymphocytes is involved in the development of chronic inflammatory disorders. Previously we have shown that the anti-inflammatory drug sulfasalazine induces apoptosis in a...

Cyclophilin A participates in the nuclear translocation of apoptosis-inducing factor in neurons after cerebral hypoxia-ischemia

Zhu, Changlian, Wang, Xiaoyang, Deinum, Johanna, Huang, Zhiheng, Gao, Jianfeng, Modjtahedi, Nazanine, ...

Upon cerebral hypoxia-ischemia (HI), apoptosis-inducing factor (AIF) can move from mitochondria to nuclei, participate in chromatinolysis, and contribute to the execution of cell death. Previous work...

Inhibition of Chk1 Kills Tetraploid Tumor Cells through a p53-Dependent Pathway

Vitale, Ilio, Galluzzi, Lorenzo, Vivet, Sonia, Nanty, Lisa, Dessen, Philippe, Senovilla, Laura, ...

Tetraploidy constitutes an adaptation to stress and an intermediate step between euploidy and aneuploidy in oncogenesis. Tetraploid cells are particularly resistant against genotoxic stress including...

An AIF orthologue regulates apoptosis in yeast

Wissing, Silke, Ludovico, Paula, Herker, Eva, Büttner, Sabrina, Engelhardt, Silvia M., Decker, Thorsten, ...

Apoptosis-inducing factor (AIF), a key regulator of cell death, is essential for normal mammalian development and participates in pathological apoptosis. The proapoptotic nature of AIF and its mode...

Essential role of p53 phosphorylation by p38 MAPK in apoptosis induction by the HIV-1 envelope

Perfettini, Jean-Luc, Castedo, Maria, Nardacci, Roberta, Ciccosanti, Fabiola, Boya, Patricia, Roumier, Thomas, ...

The proapoptotic activity of the transcription factor p53 critically depends on the phosphorylation of serine 46 (p53S46P). Here, we show that syncytia containing p53S46P could be detected in lymph...

Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death

Casares, Noelia, Pequignot, Marie O., Tesniere, Antoine, Ghiringhelli, François, Roux, Stéphan, Chaput, Nathalie, ...

Systemic anticancer chemotherapy is immunosuppressive and mostly induces nonimmunogenic tumor cell death. Here, we show that even in the absence of any adjuvant, tumor cells dying in response to...

Tumor cells convert immature myeloid dendritic cells into TGF-β–secreting cells inducing CD4+CD25+ regulatory T cell proliferation

Ghiringhelli, François, Puig, Pierre E., Roux, Stephan, Parcellier, Arnaud, Schmitt, Elise, Solary, Eric, ...

The mechanisms through which regulatory T cells accumulate in lymphoid organs of tumor-bearing hosts remain elusive. Our experiments indicate that the accumulation of CD4+CD25+ regulatory T cells (T...

NF-κB and p53 Are the Dominant Apoptosis-inducing Transcription Factors Elicited by the HIV-1 Envelope

Perfettini, Jean-Luc, Roumier, Thomas, Castedo, Maria, Larochette, Nathanael, Boya, Patricia, Raynal, Brigitte, ...

The coculture of cells expressing the HIV-1 envelope glycoprotein complex (Env) with cells expressing CD4 results into cell fusion, deregulated mitosis, and subsequent cell death. Here, we show that...

Developmental Expression of IL-2-Receptor Light Chain (CD25) in the Chicken Embryo

Fedecka-Bruner, Barbara, Penninger, Josef, Vaigot, Pierre, Lehmann, Anne, Martínez-A., Carlos, Kroemer, Guido

Thymocyte differentiation obeys the same fundamental principles in mammals as in avian species. This parallelism does not only affect the developmentally controlled acquisition of CD3, 4, 8, and TcR...

T-Lymphocyte Subsets in the Embryonic Spleen Undergoing a Graft-Versus-Host Reaction

Fedecka-Bruner, Barbara, Vaigot, Pierre, Désveaux-Chabrol, Jacqueline, Gendreau, Marcelle, Kroemer, Guido, Dieterlen-Lièvre, Françoise

Allogeneic immunocompetent T cells injected into chicken embryos induce a graft-versushost reaction (GVHR) whose most prominent manifestation is splenic hyperplasia. The highly inbred CC and CB...

Mitochondrial Release of Caspase-2 and -9 during the Apoptotic Process

Susin, Santos A., Lorenzo, Hans K., Zamzami, Naoufal, Marzo, Isabel, Brenner, Catherine, Larochette, Nathanael, ...

The barrier function of mitochondrial membranes is perturbed early during the apoptotic process. Here we show that the mitochondria contain a caspase-like enzymatic activity cleaving the caspase...

Two Distinct Pathways Leading to Nuclear Apoptosis

Susin, Santos A., Daugas, Eric, Ravagnan, Luigi, Samejima, Kumiko, Zamzami, Naoufal, Loeffler, Markus, ...

Apaf-1−/− or caspase-3−/− cells treated with a variety of apoptosis inducers manifest apoptosis-associated alterations including the translocation of apoptosis-inducing factor (AIF) from...

Human Immunodeficiency Virus 1 Envelope Glycoprotein Complex-Induced Apoptosis Involves Mammalian Target of Rapamycin/Fkbp12-Rapamycin–Associated Protein–Mediated P53 Phosphorylation

Castedo, Maria, Ferri, Karine F., Blanco, Julià, Roumier, Thomas, Larochette, Nathanael, Barretina, Jordi, ...

Syncytia arising from the fusion of cells expressing a lymphotropic human immunodeficiency virus (HIV)-1–encoded envelope glycoprotein complex (Env) gene with cells expressing the CD4/CXCR4 complex...

The HIV-1 Viral Protein R Induces Apoptosis via a Direct Effect on the Mitochondrial Permeability Transition Pore

Jacotot, Etienne, Ravagnan, Luigi, Loeffler, Markus, Ferri, Karine F., Vieira, Helena L.A., Zamzami, Naoufal, ...

Viral protein R (Vpr) encoded by HIV-1 is a facultative inducer of apoptosis. When added to intact cells or purified mitochondria, micromolar and submicromolar doses of synthetic Vpr cause a rapid...

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

Ferri, Karine F., Jacotot, Etienne, Blanco, Julià, Esté, José A., Zamzami, Naoufal, Susin, Santos A., ...

Syncytia arising from the fusion of cells expressing a lymphotropic HIV type 1–encoded envelope glycoprotein complex (Env) with cells expressing the CD4/CXC chemokine receptor 4 complex...

Control of Mitochondrial Membrane Permeabilization by Adenine Nucleotide Translocator Interacting with HIV-1 Viral Protein R and Bcl-2

Jacotot, Etienne, Ferri, Karine F., El Hamel, Chahrazed, Brenner, Catherine, Druillennec, Sabine, Hoebeke, Johan, ...

Viral protein R (Vpr), an apoptogenic accessory protein encoded by HIV-1, induces mitochondrial membrane permeabilization (MMP) via a specific interaction with the permeability transition pore...

The Central Executioner of Apoptosis: Multiple Connections between Protease Activation and Mitochondria in Fas/APO-1/CD95- and Ceramide-induced Apoptosis

Susin, Santos A., Zamzami, Naoufal, Castedo, Maria, Daugas, Eric, Wang, Hong-Gang, Geley, Stephan, ...

According to current understanding, cytoplasmic events including activation of protease cascades and mitochondrial permeability transition (PT) participate in the control of nuclear apoptosis....

The Permeability Transition Pore Complex: A Target for Apoptosis Regulation by Caspases and Bcl-2–related Proteins

Marzo, Isabel, Brenner, Catherine, Zamzami, Naoufal, Susin, Santos A., Beutner, Gisela, Brdiczka, Dieter, ...

Early in programmed cell death (apoptosis), mitochondrial membrane permeability increases. This is at least in part due to opening of the permeability transition (PT) pore, a multiprotein complex...

Lysosomal Membrane Permeabilization Induces Cell Death in a Mitochondrion-dependent Fashion

Boya, Patricia, Andreau, Karine, Poncet, Delphine, Zamzami, Naoufal, Perfettini, Jean-Luc, Metivier, Didier, ...

A number of diseases are due to lysosomal destabilization, which results in damaging cell loss. To investigate the mechanisms of lysosomal cell death, we characterized the cytotoxic action of two...

Apoptosis-inducing factor is involved in the regulation of caspase-independent neuronal cell death

Cregan, Sean P., Fortin, Andre, MacLaurin, Jason G., Callaghan, Steven M., Cecconi, Francesco, Yu, Seong-Woon, ...

Caspase-independent death mechanisms have been shown to execute apoptosis in many types of neuronal injury. P53 has been identified as a key regulator of neuronal cell death after acute injury such...

Functional and physical interaction between Bcl-XL and a BH3-like domain in Beclin-1

Maiuri, M Chiara, Le Toumelin, Gaëtane, Criollo, Alfredo, Rain, Jean-Christophe, Gautier, Fabien, Juin, Philippe, ...

The anti-apoptotic proteins Bcl-2 and Bcl-XL bind and inhibit Beclin-1, an essential mediator of autophagy. Here, we demonstrate that this interaction involves a BH3 domain within Beclin-1 (residues...

Viral Control of Mitochondrial Apoptosis

Galluzzi, Lorenzo, Brenner, Catherine, Morselli, Eugenia, Touat, Zahia, Kroemer, Guido

Throughout the process of pathogen–host co-evolution, viruses have developed a battery of distinct strategies to overcome biochemical and immunological defenses of the host. Thus, viruses have...