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The Mitochondrial Pathways of Apoptosis

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Advances in Mitochondrial Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 942))

Abstract

Apoptosis is a process of programmed cell death that serves as a major mechanism for the precise regulation of cell numbers, and as a defense mechanism to remove unwanted and potentially dangerous cells. Studies in nematode, Drosophila and mammals have shown that, although regulation of the cell death machinery is somehow different from one species to another, it is controlled by homologous proteins and involves mitochondria. In mammals, activation of caspases (cysteine proteases that are the main executioners of apoptosis) is under the tight control of the Bcl-2 family proteins, named in reference to the first discovered mammalian cell death regulator. These proteins mainly act by regulating the release of caspases activators from mitochondria. Although for a long time the absence of mitochondrial changes was considered as a hallmark of apoptosis, mitochondria appear today as the central executioner of apoptosis. In this chapter, we present the current view on the mitochondrial pathway of apoptosis with a particular attention to new aspects of the regulation of the Bcl-2 proteins family control of mitochondrial membrane permeabilization: the mechanisms implicated in their mitochondrial targeting and activation during apoptosis, the function(s) of the oncosuppressive protein p53 at the mitochondria and the role of the processes of mitochondrial fusion and fission.

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Notes

  1. 1.

    A search in PubMed database, with “p53” as query target, returns more than 52,000 results as of February 2010.

Abbreviations

ANT:

adenine nucleotide translocase

Bcl-2:

B-cell lymphoma 2

BH:

Bcl-2 homology

BOP:

BH3 only protein

CARD:

caspase activation and recruitment domain

caspase:

cysteine aspartase

CED:

cell death

DED:

death effector domain

Dronc:

Drosophila nedd-2 like caspase

EGL-1:

egg-laying-1

IAP:

inhibitor of apoptosis protein

MOMP:

mitochondrial outer membrane permeabilization

PTP:

permeability transition pore

TOM:

translocase of the outer membrane

VDAC:

voltage-dependent anion channel

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Acknowledgments

We gratefully acknowledge Sébastien Gaumer for his critical reading of the manuscript. The work of the authors was supported in part by grants from the “Association pour la Recherche Contre le Cancer” and the “Ligue Nationale Contre le Cancer”.

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Authors and Affiliations

  1. Faculté Créteil Henri Mondor, Institut National de la Sante et de la Recherche Médicale, U955, 8 Rue du Général Sarrail, 94010, Créteil, France

    Jérome Estaquier

  2. Centre de Recherche en Cancérologie Nantes Angers (UMR 892 INSERM et 6299 CNRS/Université de Nantes), 9 Quai Moncousu, 44007, Nantes, France

    François Vallette

  3. Laboratoire de Génétique et Biologie Cellulaire, EA4589, Université Versailles St-Quentin, Ecole Pratique des Hautes Etudes, 45 av des Etats-Unis, 78035, Versailles cedex, France

    Jean-Luc Vayssiere & Bernard Mignotte

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  1. Jérome Estaquier
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  2. François Vallette
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  3. Jean-Luc Vayssiere
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  4. Bernard Mignotte
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Correspondence to Bernard Mignotte .

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  1. School of Medicine, Institute of Biochemistry and Clinical B, Catholic University, Largo A. Gemelli 8, Rome, 00168, Italy

    Roberto Scatena

  2. School of Medicine, Institute of Biochemistry and Clinical B, Catholic University, Largo A. Gemelli 8, Rome, 00168, Italy

    Patrizia Bottoni

  3. School of Medicine, Institute of Biochemistry and Clinical B, Catholic University, Largo A. Gemelli 8, Rome, 00168, Italy

    Bruno Giardina

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Estaquier, J., Vallette, F., Vayssiere, JL., Mignotte, B. (2012). The Mitochondrial Pathways of Apoptosis. In: Scatena, R., Bottoni, P., Giardina, B. (eds) Advances in Mitochondrial Medicine. Advances in Experimental Medicine and Biology, vol 942. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2869-1_7

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