التفاصيل البيبلوغرافية
| العنوان: |
BCL-xL Regulates ATP Synthase and Synaptic Efficiency |
| المؤلفون: |
Laura Bonanni, Elizabeth A. Jonas, Kambiz N. Alavian, Lu Zeng, Leon P. Collis, Christoph Rahner, Hongmei Li, J. Marie Hardwick |
| المصدر: |
ResearcherID |
| بيانات النشر: |
Biophysical Society. Published by Elsevier Inc. |
| مصطلحات موضوعية: |
biology, ATP synthase, biology.protein, Biophysics, V-ATPase, Inner membrane, Bcl-xL, Patch clamp, Metabolism, Bacterial outer membrane, ATP synthase alpha/beta subunits, Cell biology |
| الوصف: |
Anti-apoptotic BCL-2 family proteins such as BCL-xL play a crucial role in protecting cells from death. High levels of expression of BCL-xL are also key to the maintenance of life of certain cancer cells. Healthy adult neurons also contain high levels of BCL-xL, suggesting that BCL-xL plays a role in daily neuronal function. We have found previously that over-expression of BCL-xL in cultured neurons causes an increase in the number and size of synapses and an increase in synaptic activity, providing evidence that BCL-xL causes long term changes in synaptic efficacy and structure. We now describe that in cultured hippocampal neurons, BCL-xL overexpression enhances the availability of total cellular ATP by increasing the ATP/ADP ratio. BCL-xL specifically enhances mitochondrial ATP production even while producing a marked decrease in cellular oxygen use. Although BCL-xL is usually thought to function in the mitochondrial outer membrane, our findings suggest that it creates an increase in the efficiency of cellular energy metabolism by direct protein-protein interaction with the ATP synthase beta subunit at the inner membrane. We find that recombinant BCL-xL protein increases native brain ATP synthase enzymatic activity and that pharmacological inhibitors of BCL-xL decrease the enzymatic activity of the synthase complex. In patch clamp recordings of the isolated synthasomes, ATP seals a membrane ion leak that could decrease synthase efficiency. In contrast, BCL-xL inhibitors increase the leak. The leak is different from the oligomycin-sensitive H+ ion pathway, and is not sensitive to the membrane permeant ANT inhibitor, bongkrekic acid, or to inhibitors of MitoKATP. Our findings suggest that BCL-xL improves the efficiency of mitochondrial metabolism by helping to seal a leak in the ATP synthase complex. This may allow for increased synthesis of synaptic components during long term increases in synaptic activity. |
| اللغة: |
English |
| تدمد: |
0006-3495 |
| DOI: |
10.1016/j.bpj.2009.12.2527 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::72fd56b163c481a49711eaf1243b72d2 |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....72fd56b163c481a49711eaf1243b72d2 |
| قاعدة البيانات: |
OpenAIRE |