[Frontiers in Bioscience 14, 3563-3570, January 1, 2009]

The mitochondrial outer membrane protein import machinery: a new player in apoptosis?

Elise Petit 1,2, Lisa Oliver1,2, Francois M. Vallette1,2

1Equipe 9, Centre de Recherche en Cancerologie Nantes-Angers (U892 INSERM), 2Faculty of Medicine, University of Nantes, 9 quai Moncousu, 44035 Nantes, cedex 01, France

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Activation and mitochondrial targeting of proteins of the BCL-2 family
3.1. Activation and mitochondrial targeting of the multidomain pro-apoptotic proteins Bax and Bak
3.2. Activation and mitochondrial targeting of the multidomain anti-apoptotic proteins Bcl-2 and Bcl-Xl.
4. Protein import across MOM
5. Interaction between members of the BCL-2 family and mitochondrial proteins
6. Concluding remarks
7. Acknowledgements
8. References

1. ABSTRACT

The proteins of the BCL-2 family (pBCL-2s) are involved in the sequence of events that culminates in apoptosis, a type I cell death program. The mitochondrion is the primary site of action of pBCL-2s and represents the cross roads between the initiation and the execution phases of apoptosis. pBCL-2s are either constitutively associated with the mitochondria outer membrane (MOM) or targeted to this membrane at the onset of apoptosis. The mechanisms implicated in their targeting and activation during apoptosis is largely unknown. Recently, several pBCL-2s have been shown to interact with components of the translocase of the outer membrane (TOM), a complex responsible for the import into and across the MOM of nuclear encoded mitochondrial proteins. Here we will review the available data and discuss the possible implications of this interaction in the apoptotic programme.