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dc.contributor.authorAlavian, Kambiz N.
dc.contributor.authorLi, Hongmei
dc.contributor.authorCollis, Leon P.
dc.contributor.authorBonanni, Laura
dc.contributor.authorZeng, Lu
dc.contributor.authorSacchetti, Silvio
dc.contributor.authorLazrove, Emma
dc.contributor.authorNabili, Panah
dc.contributor.authorFlaherty, Benjamin
dc.contributor.authorGraham, Morven
dc.contributor.authorChen, Yingbei
dc.contributor.authorMesserli, Shanta M.
dc.contributor.authorMariggio, Maria A.
dc.contributor.authorRahner, Christoph
dc.contributor.authorMcNay, Ewan
dc.contributor.authorShore, Gordon
dc.contributor.authorSmith, Peter J. S.
dc.contributor.authorHardwick, J. Marie
dc.contributor.authorJonas, Elizabeth A.
dc.date.accessioned2011-11-30T13:58:59Z
dc.date.available2012-03-18T08:32:56Z
dc.date.issued2011-06
dc.identifier.urihttp://hdl.handle.net/1912/4905
dc.descriptionAuthor 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.abstractAnti-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.sponsorshipThis work was supported by NIH NS064967 (E.A.J.) and NS37402 (JMH).en_US
dc.format.mimetypeapplication/pdf
dc.language.isoen_USen_US
dc.relation.urihttp://dx.doi.org/10.1038/ncb2330
dc.titleBcl-xL regulates metabolic efficiency of neurons through interaction with the mitochondrial F1FO ATP synthaseen_US
dc.typePreprinten_US


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