Medical College of Wisconsin
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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 01;276(22):19414-9

Date

03/22/2001

Pubmed ID

11259441

DOI

10.1074/jbc.M101590200

Abstract

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.

Author List

Vander Heiden MG, Li XX, Gottleib E, Hill RB, Thompson CB, Colombini M

Author

Ronald Blake Hill PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Diphosphate
Animals
Apoptosis
Cell Line
Cell Membrane
Cell Survival
Cytochrome c Group
Diffusion
Electrophysiology
Humans
Intracellular Membranes
Kinetics
Mice
Mitochondria, Liver
NAD
Oxygen
Permeability
Phosphocreatine
Phosphorylation
Porins
Protein Binding
Protein Conformation
Proto-Oncogene Proteins c-bcl-2
Rats
Recombinant Proteins
Time Factors
Voltage-Dependent Anion Channels
bcl-X Protein
jenkins-FCD Prod-399 190a069c593fb5498b7fcd942f44b7bc9cdc7ea1