Abstract
Anti-apoptotic Bcl2 family proteins such as Bcl-x(L) protect cells from death by sequestering apoptotic molecules, but also contribute to normal neuronal function. We find in hippocampal neurons that Bcl-x(L) enhances the efficiency of energy metabolism. Our evidence indicates that Bcl-x(L)interacts directly with the β-subunit of the F(1)F(O) ATP synthase, decreasing an ion leak within the F(1)F(O) ATPase complex and thereby increasing net transport of H(+) by F(1)F(O) during F(1)F(O) ATPase activity. By patch clamping submitochondrial vesicles enriched in F(1)F(O) ATP synthase complexes, we find that, in the presence of ATP, pharmacological or genetic inhibition of Bcl-x(L) activity increases the membrane leak conductance. In addition, recombinant Bcl-x(L) protein directly increases the level of ATPase activity of purified synthase complexes, and inhibition of endogenous Bcl-x(L) decreases the level of F(1)F(O) enzymatic activity. Our findings indicate that increased mitochondrial efficiency contributes to the enhanced synaptic efficacy found in Bcl-x(L)-expressing neurons.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenosine Triphosphate / metabolism
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Animals
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Biphenyl Compounds / pharmacology
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Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / pharmacology
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Cells, Cultured
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Energy Metabolism* / drug effects
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Enzyme Inhibitors / pharmacology
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Hippocampus / cytology
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Hippocampus / drug effects
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Hippocampus / enzymology*
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Hydrolysis
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Membrane Potential, Mitochondrial
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Mitochondria / drug effects
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Mitochondria / enzymology*
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Mitochondrial Membranes / enzymology
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Mitochondrial Proton-Translocating ATPases / antagonists & inhibitors
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Mitochondrial Proton-Translocating ATPases / metabolism*
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Neurons / drug effects
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Neurons / enzymology*
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Nitrophenols / pharmacology
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Oligomycins / pharmacology
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Oxygen Consumption
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Patch-Clamp Techniques
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Piperazines / pharmacology
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Proton Ionophores / pharmacology
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RNA Interference
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Rats
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Recombinant Fusion Proteins / metabolism
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Sulfonamides / pharmacology
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Synapses / drug effects
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Synapses / enzymology*
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Time Factors
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Transfection
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bcl-2 Homologous Antagonist-Killer Protein / metabolism
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bcl-2-Associated X Protein / metabolism
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bcl-X Protein / antagonists & inhibitors
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bcl-X Protein / genetics
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bcl-X Protein / metabolism*
Substances
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ABT-737
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Bak1 protein, rat
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Bax protein, rat
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Bcl2l1 protein, rat
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Biphenyl Compounds
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Enzyme Inhibitors
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Nitrophenols
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Oligomycins
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Piperazines
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Proton Ionophores
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Recombinant Fusion Proteins
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Sulfonamides
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bcl-2 Homologous Antagonist-Killer Protein
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bcl-2-Associated X Protein
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bcl-X Protein
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Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone
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Adenosine Triphosphate
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Mitochondrial Proton-Translocating ATPases