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 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.
Original language | English (US) |
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Pages (from-to) | 1224-1233 |
Number of pages | 10 |
Journal | Nature Cell Biology |
Volume | 13 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2011 |
Externally published | Yes |
ASJC Scopus subject areas
- Cell Biology