| First Author | Alavian KN | Year | 2011 |
| Journal | Nat Cell Biol | Volume | 13 |
| Issue | 10 | Pages | 1224-33 |
| PubMed ID | 21926988 | Mgi Jnum | J:176954 |
| Mgi Id | MGI:5293238 | Doi | 10.1038/ncb2330 |
| Citation | Alavian KN, et al. (2011) Bcl-x(L) regulates metabolic efficiency of neurons through interaction with the mitochondrial F(1)F(O) ATP synthase. Nat Cell Biol 13(10):1224-33 |
| abstractText | 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 beta-subunit of the F(1)F(O) ATP synthase, decreasing an ion leak within the F(1)F(O) ATPase complex and thereby increasing net transport of H(+) by F(1)F(O) during F(1)F(O) ATPase activity. By patch clamping submitochondrial vesicles enriched in F(1)F(O) ATP synthase complexes, we find that, in the presence of ATP, pharmacological or genetic inhibition of Bcl-x(L) 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-x(L) decreases the level of F(1)F(O) enzymatic activity. Our findings indicate that increased mitochondrial efficiency contributes to the enhanced synaptic efficacy found in Bcl-x(L)-expressing neurons. |
