TOM22, a core component of the mitochondria outer membrane protein translocation pore, is a mitochondrial receptor for the proapoptotic protein Bax

G Bellot; P-F Cartron; E Er; L Oliver; P Juin; L C Armstrong; P Bornstein; K Mihara; S Manon; F M Vallette

doi:10.1038/sj.cdd.4402055

TOM22, a core component of the mitochondria outer membrane protein translocation pore, is a mitochondrial receptor for the proapoptotic protein Bax

Cell Death Differ. 2007 Apr;14(4):785-94. doi: 10.1038/sj.cdd.4402055. Epub 2006 Nov 10.

Authors

G Bellot¹, P-F Cartron, E Er, L Oliver, P Juin, L C Armstrong, P Bornstein, K Mihara, S Manon, F M Vallette

Affiliation

¹ INSERM U601, Université de Nantes, Faculté de Médecine, Nantes Cedex, France.

PMID: 17096026
DOI: 10.1038/sj.cdd.4402055

Abstract

The association of Bax with mitochondria is an essential step in the implementation of apoptosis. By using a bacterial two-hybrid assay and crosslinking strategies, we have identified TOM22, a component of the translocase of the outer mitochondrial membrane (TOM), as a mitochondrial receptor of Bax. Peptide mapping showed that the interaction of Bax with TOM22 involved the first alpha helix of Bax and possibly two central alpha helices, which are homologous to the pore forming domains of some toxins. Antibodies directed against TOM22 or an antisense knockdown of the expression of TOM22 specifically inhibited the association of Bax with mitochondria and prevented Bax-dependent apoptosis. In yeast, a haploid strain for TOM22 exhibited a decreased expression of TOM22 and mitochondrial association of ectopically expressed human Bax. Our data provide a new perspective on the mechanism of association of Bax with mitochondria as it involves a classical import pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / physiology
Gene Silencing
Glioblastoma
Glioma
Humans
Membrane Transport Proteins / metabolism*
Microscopy, Confocal
Mitochondria, Liver / metabolism*
Mitochondrial Membrane Transport Proteins / chemistry
Mitochondrial Membrane Transport Proteins / genetics*
Mitochondrial Membrane Transport Proteins / metabolism*
Mitochondrial Membranes / metabolism*
Mitochondrial Precursor Protein Import Complex Proteins
Mitochondrial Proteins / metabolism
Protein Binding / physiology
Protein Transport / physiology
Rats
Receptors, Cell Surface
Receptors, Cytoplasmic and Nuclear / metabolism
Saccharomyces cerevisiae Proteins / metabolism*
Tumor Cells, Cultured
Voltage-Dependent Anion Channels / metabolism*
bcl-2-Associated X Protein / deficiency
bcl-2-Associated X Protein / metabolism*

Substances

Membrane Transport Proteins
Mitochondrial Membrane Transport Proteins
Mitochondrial Precursor Protein Import Complex Proteins
Mitochondrial Proteins
Receptors, Cell Surface
Receptors, Cytoplasmic and Nuclear
Saccharomyces cerevisiae Proteins
TOM22 protein, S cerevisiae
Tomm20 protein, rat
Voltage-Dependent Anion Channels
bcl-2-Associated X Protein