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The cell biology of apoptosis: Evidence for the implication of mitochondria

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Abstract

The apoptotic process can be subdivided into three phases: a death-stimulus-dependent heterogeneous induction phase, a common effector phase during which the central apoptotic executioner is activated, and a common degradation phase during which cells acquire the biochemical and morphological features of end-stage apoptosis. Recently, it has become clear that the central apoptosis executioner is dictated by cytoplasmic (non-nuclear) events and that nuclear changes that define apoptosis (chromatin condensation and oligonucleosomal DNA fragmentation) only become manifest beyond the point-of-no-return of apoptosis, during the late degradation phase. It appears that one obligatory event of the apoptotic cascade involves a characteristic change in mitochondrial function, namely the so-called mitochondrial permeability transition. Permeability transition leading to disruption of the mitochondrial transmembrane potential precedes nuclear and plasma membrane features of apoptosis. Induction of permeability transition in cells suffices to cause the full-blown picture of apoptosis. In vitro induction of permeability transition in isolated mitochondria provokes the release of a factor capable of inducing apoptotic changes in isolated nuclei. Permeability transition is subject to regulation by multiple endogenous effectors, including members of the bcl-2 gene family. Its inhibition by pharmacological agents or hyperexpression of Bcl-2 prevents apoptosis, indicating that PT is a central coordinating event of the apoptotic effector stage.

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  1. Centre National de la Recherche Scientifique-UPR420, 19 rue Guy Môquet, B.P.8, F-94801, Villejuif, France

    S. A. Susin, N. Zamzami & G. Kroemer Dr

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  1. S. A. Susin
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Supported by ARC, ANRS, CNRS, FRM, Fondation de France, INSERM, NATO, Ligue contre le Cancer. Ministère de la Recherche et de l'Industrie (France), and Sidaction (to GK). SAS receives a fellowship from the Spanish Government (Ministerio de Ciencia y Educación).

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Susin, S.A., Zamzami, N. & Kroemer, G. The cell biology of apoptosis: Evidence for the implication of mitochondria. Apoptosis 1, 231–242 (1996). https://doi.org/10.1007/BF00143316

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