Bcl-2 and porin follow different pathways of TOM-dependent insertion into the mitochondrial outer membrane

J Mol Biol. 2002 Nov 1;323(4):729-38. doi: 10.1016/s0022-2836(02)00995-6.

Abstract

The bcl-2 gene encodes a 26kDa protein which functions as a central regulator of apoptosis. Here we investigated the pathway of Bcl-2alpha into the mitochondrial outer membrane using the yeast Saccharomyces cerevisiae as a model organism. We found that interactions of Bcl-2alpha with the mitochondrial import receptor Tom20 are dependent on two positively charged lysine residues in the immediate vicinity of the carboxy-terminal hydrophobic membrane anchor. The targeting function of these residues is independent of Tom22. Subsequent insertion of Bcl-2alpha into the mitochondrial outer membrane does not require Tom5 or Tom40, indicating that Bcl-2alpha bypasses the general import pore (GIP). Bcl-2alpha shows a unique pattern of interactions with the components of the mitochondrial TOM complex, demonstrating that at least two different pathways lead from the import receptor Tom20 into the mitochondrial outer membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Transport, Active
  • Humans
  • Intracellular Membranes / metabolism*
  • Lysine / metabolism
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins*
  • Mitochondria / metabolism*
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins
  • Porins / metabolism*
  • Protein Transport
  • Proto-Oncogene Proteins c-bcl-2 / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Rats
  • Receptors, Cell Surface*
  • Receptors, Cytoplasmic and Nuclear*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Time Factors
  • Voltage-Dependent Anion Channels

Substances

  • Membrane Proteins
  • Membrane Transport Proteins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins
  • Porins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Saccharomyces cerevisiae Proteins
  • TOM20 protein, S cerevisiae
  • TOM22 protein, S cerevisiae
  • TOMM20 protein, human
  • TOMM22 protein, human
  • Tomm20 protein, rat
  • Voltage-Dependent Anion Channels
  • Lysine