Bcl-xL prevents cell death following growth factor withdrawal by facilitating mitochondrial ATP/ADP exchange

Mol Cell. 1999 Feb;3(2):159-67. doi: 10.1016/s1097-2765(00)80307-x.


Growth factor withdrawal is associated with a metabolic arrest that can result in apoptosis. Cell death is preceded by loss of outer mitochondrial membrane integrity and cytochrome c release. These mitochondrial events appear to follow a relative increase in mitochondrial membrane potential. This change in membrane potential results from the failure of the adenine nucleotide translocator (ANT)/voltage-dependent anion channel (VDAC) complex to maintain ATP/ADP exchange. Bcl-xL expression allows growth factor-deprived cells to maintain sufficient mitochondrial ATP/ADP exchange to sustain coupled respiration. These data demonstrate that mitochondrial adenylate transport is under active regulation. Efficient exchange of ADP for ATP is promoted by Bcl-xL expression permitting oxidative phosphorylation to be regulated by cellular ATP/ADP levels and allowing mitochondria to adapt to changes in metabolic demand.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Diphosphate / metabolism*
  • Adenosine Triphosphate / metabolism*
  • Animals
  • Apoptosis / physiology*
  • Biological Transport, Active
  • Caspase Inhibitors
  • Fluorescent Dyes
  • Gramicidin / pharmacology
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism
  • Interleukin-3 / pharmacology*
  • Membrane Potentials
  • Mice
  • Mitochondria / metabolism*
  • Oxidative Phosphorylation / drug effects
  • Oxygen Consumption / drug effects
  • Porins / physiology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Recombinant Fusion Proteins / physiology
  • Rhodamine 123
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Transfection
  • Tumor Cells, Cultured / drug effects
  • Voltage-Dependent Anion Channels
  • bcl-X Protein


  • Bcl2l1 protein, mouse
  • Caspase Inhibitors
  • Fluorescent Dyes
  • Interleukin-3
  • Porins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • Voltage-Dependent Anion Channels
  • bcl-X Protein
  • Gramicidin
  • Rhodamine 123
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Sodium-Potassium-Exchanging ATPase