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
03/22/2001Pubmed ID
11259441DOI
10.1074/jbc.M101590200Scopus ID
2-s2.0-0035380462 (requires institutional sign-in at Scopus site) 336 CitationsAbstract
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 MMESH terms used to index this publication - Major topics in bold
Adenosine DiphosphateAnimals
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