Bcl-x L regulates metabolic efficiency of neurons through interaction with the mitochondrial F1 FO ATP synthase

Kambiz N. Alavian, Hongmei Li, Leon Collis, Laura Bonanni, Lu Zeng, Silvio Sacchetti, Emma Lazrove, Panah Nabili, Benjamin Flaherty, Morven Graham, Yingbei Chen, Shanta M. Messerli, Maria A. Mariggio, Christoph Rahner, Ewan McNay, Gordon C. Shore, Peter J.S. Smith, J. Marie Hardwick, Elizabeth A. Jonas

Research output: Contribution to journalArticlepeer-review

Abstract

Anti-apoptotic Bcl2 family proteins such as Bcl-x L protect cells from death by sequestering apoptotic molecules, but also contribute to normal neuronal function. We find in hippocampal neurons that Bcl-x L enhances the efficiency of energy metabolism. Our evidence indicates that Bcl-x L interacts directly with the β-subunit of the F1 FO ATP synthase, decreasing an ion leak within the F1 FO ATPase complex and thereby increasing net transport of H + by F1 FO during F1 FO ATPase activity. By patch clamping submitochondrial vesicles enriched in F 1 FO 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-x L protein directly increases the level of ATPase activity of purified synthase complexes, and inhibition of endogenous Bcl-xL decreases the level of F1 FO enzymatic activity. Our findings indicate that increased mitochondrial efficiency contributes to the enhanced synaptic efficacy found in Bcl-x L-expressing neurons.

Original languageEnglish (US)
Pages (from-to)1224-1233
Number of pages10
JournalNature cell biology
Volume13
Issue number10
DOIs
StatePublished - Oct 2011

ASJC Scopus subject areas

  • Cell Biology

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