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.

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 Proteins / metabolism
  • Protein Binding / physiology
  • Protein Transport / physiology
  • Rats
  • 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 Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Saccharomyces cerevisiae Proteins
  • TOM22 protein, S cerevisiae
  • Tomm20 protein, rat
  • Voltage-Dependent Anion Channels
  • bcl-2-Associated X Protein