Author: ["Kambiz N. Alavian","Hongmei Li","Leon Collis","Laura Bonanni","Lu Zeng","Silvio Sacchetti","Emma Lazrove","Panah Nabili","Benjamin Flaherty","Morven Graham","Yingbei Chen","Shanta M. Messerli","Maria A. Mariggio","Christoph Rahner","Ewan McNay","Gordon C. Shore","Peter J. S. Smith","J. Marie Hardwick","Elizabeth A. Jonas"]
CITE.CC academic search helps you expand the influence of your papers.
Abstract
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 find in hippocampal neurons that Bcl-xL enhances the efficiency of energy metabolism. Our evidence indicates that Bcl-xLinteracts directly with the β-subunit of the F1FO ATP synthase, decreasing an ion leak within the F1FO ATPase complex and thereby increasing net transport of H+ by F1FO during F1FO ATPase activity. By patch clamping submitochondrial vesicles enriched in F1FO 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-xL protein directly increases the level of ATPase activity of purified synthase complexes, and inhibition of endogenous Bcl-xL decreases the level of F1FO enzymatic activity. Our findings indicate that increased mitochondrial efficiency contributes to the enhanced synaptic efficacy found in Bcl-xL-expressing neurons. ATP production by mitochondria requires the efficient flow of protons through the F1FO ATP-synthase complex. Jonas and colleagues show that Bcl-xL interacts with the F1FO complex in the mitochondrial matrix and increases the efficiency of this enzyme by decreasing proton leak.Cite this article
Alavian, K., Li, H., Collis, L. et al. Bcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase. Nat Cell Biol 13, 1224–1233 (2011). https://doi.org/10.1038/ncb2330 