Bcl-xl regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FoATP synthase
Alavian, Kambiz N., Li, Hongmei, Collis, Leon, Bonanni, Laura, Zeng, Lu, Sacchetti, Silvio, Lazrove, Emma, Nabili, Panah, Flaherty, Benjamin, Graham, Morven, Chen, Yingbei, Messerli, Shanta M., Mariggio, Maria A., Rahner, Christopher, McNay, Ewan, Shore, Gordon C., Smith, Peter J.S., Hardwick, J. Marie and Jonas, Elizabeth A. (2011) Bcl-xl regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FoATP synthase. Nature Cell Biology, 13, (10), 1224-1233. (doi:10.1038/ncb2330) (PMID:21926988)
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Description/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.
| Item Type: | Article |
|---|---|
| ISSN: | 1465-7392 (print) 1476-4679 (electronic) |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| Divisions: | Faculty of Natural and Environmental Sciences > Biological Sciences |
| ePrint ID: | 195555 |
| URI: | http://eprints.soton.ac.uk/id/eprint/195555 |
| Deposited On: | 28 Oct 2011 10:26 |
| Last Modified: | 28 Nov 2011 14:33 |
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