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

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dc.contributor.author Alavian, Kambiz N.
dc.contributor.author Li, Hongmei
dc.contributor.author Collis, Leon P.
dc.contributor.author Bonanni, Laura
dc.contributor.author Zeng, Lu
dc.contributor.author Sacchetti, Silvio
dc.contributor.author Lazrove, Emma
dc.contributor.author Nabili, Panah
dc.contributor.author Flaherty, Benjamin
dc.contributor.author Graham, Morven
dc.contributor.author Chen, Yingbei
dc.contributor.author Messerli, Shanta M.
dc.contributor.author Mariggio, Maria A.
dc.contributor.author Rahner, Christoph
dc.contributor.author McNay, Ewan
dc.contributor.author Shore, Gordon
dc.contributor.author Smith, Peter J. S.
dc.contributor.author Hardwick, J. Marie
dc.contributor.author Jonas, Elizabeth A.
dc.date.accessioned 2011-11-30T13:58:59Z
dc.date.available 2012-03-18T08:32:56Z
dc.date.issued 2011-06
dc.identifier.uri http://hdl.handle.net/1912/4905
dc.description Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Cell Biology 13 (2011): 1224–1233, doi:10.1038/ncb2330. en_US
dc.description.abstract Anti-apoptotic BCL-2 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 suggests that Bcl-xL interacts directly with the beta 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 increases the membrane leak conductance. In addition, recombinant Bcl-xL protein directly increases ATPase activity of purified synthase complexes, while inhibition of endogenous Bcl-xL decreases F1FO enzymatic activity. Our findings suggest that increased mitochondrial efficiency contributes to the enhanced synaptic efficacy found in Bcl-xL expressing neurons. en_US
dc.description.sponsorship This work was supported by NIH NS064967 (E.A.J.) and NS37402 (JMH). en_US
dc.format.mimetype application/pdf
dc.language.iso en_US en_US
dc.relation.uri http://dx.doi.org/10.1038/ncb2330
dc.title Bcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthase en_US
dc.type Preprint en_US


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