Bcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase

Anti-apoptotic Bcl2 family proteins such as Bcl-xL protect cells from death by sequestering apoptotic molecules, but also contribute to normal neuronal function. We nd in hippocampal neurons that Bcl-xL enhances the efciency of energy metabolism. Our evidence indicates that Bcl-xLinteracts directly with the -subunit of the F1FO ATP synthase, decreasing an ion leak within the F1FO ATPase complex and thereby increasing net transport of HC by F1FO during F1FO ATPase activity. By patch clamping submitochondrial vesicles enriched in F1FO ATP synthase complexes, we nd that, in the presence of ATP, pharmacological or genetic inhibition of Bcl-xL activity increases the membrane leak conductance. In addition, recombinant Bcl-xL protein directly increases the level of ATPase activity of puried synthase complexes, and inhibition of endogenous Bcl-xL decreases the level of F1FO enzymatic activity. Our ndings indicate that increased mitochondrial efciency contributes to the enhanced synaptic efficacy found in Bcl-xL-expressing neurons.