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 F1 FO ATP synthase, decreasing an ion leak within the F1 FO ATPase complex and thereby increasing net transport of H + by F1 FO during F1 FO ATPase activity. By patch clamping submitochondrial vesicles enriched in F 1 FO ATP synthase complexes, we find that, in the presence of ATP, pharmacological or genetic inhibition of Bcl-xL 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-xL decreases the level of F1 FO enzymatic activity. Our findings indicate that increased mitochondrial efficiency contributes to the enhanced synaptic efficacy found in Bcl-x L-expressing neurons.
ASJC Scopus subject areas
- Cell Biology