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

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Date
2011-06Author
Alavian, Kambiz N.
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Li, Hongmei
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Collis, Leon P.
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Bonanni, Laura
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Zeng, Lu
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Sacchetti, Silvio
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Lazrove, Emma
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Nabili, Panah
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Flaherty, Benjamin
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Graham, Morven
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Chen, Yingbei
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Messerli, Shanta M.
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Mariggio, Maria A.
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Rahner, Christoph
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McNay, Ewan
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Shore, Gordon
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Smith, Peter J. S.
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Hardwick, J. Marie
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Jonas, Elizabeth A.
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https://hdl.handle.net/1912/4905As published
https://doi.org/10.1038/ncb2330Abstract
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.
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.