Bcl-xL promotes the open configuration of the voltage-dependent anion channel and metabolite passage through the outer mitochondrial membrane

J Biol Chem. 2001 Jun 1;276(22):19414-9. doi: 10.1074/jbc.M101590200. Epub 2001 Mar 20.


The diffusion of metabolites across the outer mitochondrial membrane is essential for coupled cellular respiration. The outer membrane of mitochondria isolated from growth factor-deprived cells is impaired in its ability to exchange metabolic anions. When added to mitochondria, recombinant Bcl-x(L) restores metabolite exchange across the outer membrane without inducing the loss of cytochrome c from the intermembrane space. Restoration of outer membrane permeability to anionic metabolites does not occur directly through Bcl-x(L) ion channels. Instead, recombinant Bcl-x(L) maintains the outer mitochondrial membrane channel, VDAC, in an open configuration. Consistent with these findings, when ADP-induced oxidative phosphorylation is limited by exogenous beta-NADH, recombinant Bcl-x(L) can sustain outer mitochondrial membrane permeability to ADP. beta-NADH limits respiration by promoting the closed configuration of VDAC. Together these results demonstrate that following an apoptotic signal, Bcl-x(L) can maintain metabolite exchange across the outer mitochondrial membrane by inhibiting VDAC closure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Animals
  • Apoptosis
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Survival
  • Cytochrome c Group / metabolism
  • Diffusion
  • Electrophysiology
  • Humans
  • Intracellular Membranes / metabolism
  • Kinetics
  • Mice
  • Mitochondria, Liver / metabolism
  • NAD / metabolism
  • Oxygen / metabolism
  • Permeability
  • Phosphocreatine / metabolism
  • Phosphorylation
  • Porins / chemistry*
  • Porins / metabolism*
  • Protein Binding
  • Protein Conformation
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Rats
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Time Factors
  • Voltage-Dependent Anion Channels
  • bcl-X Protein


  • BCL2L1 protein, human
  • Bcl2l1 protein, mouse
  • Bcl2l1 protein, rat
  • Cytochrome c Group
  • Porins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • Voltage-Dependent Anion Channels
  • bcl-X Protein
  • Phosphocreatine
  • NAD
  • Adenosine Diphosphate
  • Oxygen