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Sylvie Montessuit,
Syam Prakash Somasekharan,
Oihana Terrones, Safa Lucken-Ardjomande,
Sébastien Herzig,
Robert Schwarzenbacher,
Dietmar J Manstein,
Ella Bossy-Wetzel,
Gorka Basañez,
Paolo Meda,
Jean-Claude Martinou
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ABSTRACT: In response to many apoptotic stimuli, oligomerization of Bax is essential for mitochondrial outer membrane permeabilization and the ensuing release of cytochrome c. These events are accompanied by mitochondrial fission that appears to require Drp1, a large GTPase of the dynamin superfamily. Loss of Drp1 leads to decreased cytochrome c release by a mechanism that is poorly understood. Here we show that Drp1 stimulates tBid-induced Bax oligomerization and cytochrome c release by promoting tethering and hemifusion of membranes in vitro. This function of Drp1 is independent of its GTPase activity and relies on arginine 247 and the presence of cardiolipin in membranes. In cells, overexpression of Drp1 R247A/E delays Bax oligomerization and cell death. Our findings uncover a function of Drp1 and provide insight into the mechanism of Bax oligomerization.
Cell 09/2010; 142(6):889-901. · 32.40 Impact Factor
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ABSTRACT: The induction of caspase-independent cell death by killer lymphocytes involves the serine protease granzyme A (GzmA). In this issue, Martinvalet et al. (2008) show that GzmA penetrates the mitochondrial matrix without perturbing normal mitochondrial functions. In the mitochondrial matrix, GzmA cleaves NDUFS3 (a component of the electron transport chain) leading to production of reactive oxygen species and ultimately to cell death.
Cell 06/2008; 133(4):568-70. · 32.40 Impact Factor
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ABSTRACT: In response to many apoptotic stimuli, Bcl-2 family pro-apoptotic members, such as Bax and Bak, are activated. This results in their oligomerization, permeabilization of the outer mitochondrial membrane, and release of many proteins that are normally confined in the mitochondrial inter-membrane space. Among these proteins are cytochrome c, Smac/DIABLO, OMI/HtrA2, AIF and endonuclease G. Mitochondrial outer membrane permeabilization (MOMP) is also associated with fragmentation of the mitochondrial network. The mechanisms that lead to the oligomerization of proapoptotic members of the Bcl-2 family and to MOMP are still unclear and the role of mitochondrial fission in these events remains elusive.
Novartis Foundation symposium 02/2007; 287:170-6; discussion 176-82.
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ABSTRACT: In many apoptotic responses, pro-apoptotic members of the Bcl-2 family trigger the permeabilization of the outer mitochondrial membrane, thereby allowing the release of mitochondrial apoptogenic factors that contribute to caspase activation in the cytosol. The mechanisms that lead to the activation of pro-apoptotic Bcl-2 family members and to the permeabilization of the outer mitochondrial membrane are not yet completely understood. Here, we attempt to summarize our current view of the mechanisms that lead to these events, regarding both additional proteins that were recently suggested to be involved, and the roles of lipids.
Comptes Rendus Biologies 08/2005; 328(7):616-31. · 1.53 Impact Factor
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ABSTRACT: Under stress conditions, apoptogenic factors normally sequestered in the mitochondrial intermembrane space are released into the cytosol, caspases are activated and cells die by apoptosis. Although the precise mechanism that leads to the permeabilization of mitochondria is still unclear, the activation of multidomain pro-apoptotic proteins of the Bcl-2 family, such as Bax and Bak, is evidently crucial. Regulation of Bax and Bak by other members of the family has been known for a long time, but recent evidence suggests that additional unrelated proteins participate in the process, both as inhibitors and activators. The important rearrangements mitochondrial lipids undergo during apoptosis play a role in the permeabilization process and this role is probably more central than first envisioned.
Journal of Cell Science 03/2005; 118(Pt 3):473-83. · 6.11 Impact Factor
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ABSTRACT: Mitochondria are involved in many apoptotic responses. Following permeabilization of their outer membrane, they release many apoptogenic proteins, including cytochrome c, which contribute to caspase activation. The mechanisms responsible for membrane permeability are not completely understood. Here, we briefly review the mechanisms that have been proposed to explain this phenomenon.
Journal de la Société de Biologie 01/2005; 199(3):207-10.
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ABSTRACT: Mitochondria are involved in many apoptotic responses. Following permeabilization of their outer membrane, they release many apoptogenic proteins, including cytochrome c, which contribute to caspase activation. The mechanisms responsible for membrane permeability are not completely understood. Here, we briefly review the mechanisms that have been proposed to explain this phenomenon. Les mitochondries sont impliquées dans de nombreuses voies de signalisation de l'apoptose. Suite à la perméabilisation de leur membrane externe par des membres pro-apoptotiques de la famille Bcl-2, elles libèrent plusieurs protéines apoptogènes, dont le cytochrome c, qui contribuent à l'activation des caspases. Les mécanismes responsables de la perméabilisation membranaire mitochondriale sont encore mal compris. Leur étude a abouti à la construction de plusieurs modèles qui sont analysés dans cette revue.
http://dx.doi.org/10.1051/jbio:2005021.
