Abstract
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
Substances
- 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