[Frontiers in Bioscience 14, 4127-4137, January 1, 2009]

[Frontiers in Bioscience 14, 4127-4137, January 1, 2009]

Mitochondria, Bcl-2 family proteins and apoptosomes: of worms, flies and men

Jessie Colin, Sebastien Gaumer, Isabelle Guenal, Bernard Mignotte

Universite Versailles St-Quentin, Ecole Pratique des Hautes Etudes, Centre National de la Recherche Scientifique, UMR8159, Laboratoire de Genétique et Biologie Cellulaire, 45 av des Etats-Unis 78035 Versailles cedex France

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Initiator caspases: 3.1. The nematode case: a unique caspase; 3.2. Mammalian caspase 9; 3.3. The only Drosophila CARD-carrying caspase: Dronc
4. Apical caspases activation in the mitochondrial pathway-Role of the apoptosome: 4.1. The simplest model: the worm apoptosome; 4.2. Caspase 9 activation in mammals: the apoptosome; 4.3. The most controversial: the Drosophila apoptosome
5. Bcl-2 family members and apoptosome activation: 5.1. The direct model: C. elegans Bcl-2 family members; 5.2. Permeabilization function: mammalian Bcl-2 family; 5.3. The least understood: Drosophila Bcl-2 family members
6. Concluding remarks
7. Acknowledgements
8. References

1. ABSTRACT

Initiator caspases are activated within specialized complexes, one of which is the apoptosome. The apoptosome is always constituted by at least an initiator caspase and a caspase activator. Apoptosome activation enables maturation of the associated caspase and constitutes a key step for cell fate. This activating complex is found throughout metazoans but its composition and regulation seem slightly different from one species to another. This review focuses on the composition and activation of the apoptosome in different species and details the role of mitochondrial factors and Bcl-2 family members in this activation.