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

Thumbnail Image
Alavian, Kambiz N.
Li, Hongmei
Collis, Leon P.
Bonanni, Laura
Zeng, Lu
Sacchetti, Silvio
Lazrove, Emma
Nabili, Panah
Flaherty, Benjamin
Graham, Morven
Chen, Yingbei
Messerli, Shanta M.
Mariggio, Maria A.
Rahner, Christoph
McNay, Ewan
Shore, Gordon
Smith, Peter J. S.
Hardwick, J. Marie
Jonas, Elizabeth A.
Alternative Title
Date Created
Replaced By
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.
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.
Embargo Date
Cruise ID
Cruise DOI
Vessel Name