THE ANTI-APOPTOTIC PROTEIN BCL-XL ENHANCES NEURONAL METABOLISM

抗凋亡蛋白 BCL-XL 增强神经元代谢

• 批准号: 7953836
• 负责人: Elizabeth Ann Jonas
• 金额: $ 4.48万
• 依托单位: MARINE BIOLOGICAL LABORATORY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953836
• 关键词: Apoptotic; Attenuated; Brain; Cell Death; Cell Survival; Cells; Computer Retrieval of Information on Scientific Projects Database; Cytosol; Event; Funding; Grant; Guanosine Triphosphate Phosphohydrolases; Hippocampus (Brain); Institution; Location; Membrane; Metabolism; Mitochondria; Mitochondrial Proteins; Neurons; Oxygen; Presynaptic Terminals; Process; Research; Research Personnel; Resources; Site; Source; Synapses; Transfection; United States National Institutes of Health; Vesicle; bcl-xlong protein; improved; postsynaptic; prevent; synaptogenesis

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Within a developing presynaptic terminal, maturation of vesicle pools and synaptic stabilization occur shortly after contact with the postsynaptic target cell, but little is known about the intracellular molecules that control these processes. We have shown that the major brain anti-apoptotic mitochondrial protein BCL-xL acts presynaptically in cultured hippocampal neurons to increase the number and size of vesicle clusters, and to increase spontaneous vesicle fusion events. Normal mitochondrial function is necessary for the augmentation in spontaneous synaptic events because inhibition of mitochondrial function eliminates the increase. BCL-xL transfection increases the number of mitochondria and improves mitochondrial localization to synaptic sites in part through its effects on the GTPase DRP-1. Conversly, a reduction in endogenous BCL-xL decreases synaptogenesis without attenuating cell viability. Not only does BCL-xL direct newly divided mitochondria to synaptic sites, it also enhances ATP availability within the cytosol while decreasing oxygen flux across neuronal membranes. Thus, in addition to preventing cell death in neurons, we suggest that BCL-xL enhances mitochondrial efficiency and changes mitochondrial location, and may thereby produce synaptic maturation.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在发育中的突触前末梢中，囊泡池的成熟和突触稳定在与突触后靶细胞接触后不久发生，但对控制这些过程的细胞内分子知之甚少。我们已经表明，主要的脑抗凋亡线粒体蛋白BCL-xL行为突触前在培养的海马神经元，以增加囊泡簇的数量和大小，并增加自发囊泡融合事件。正常的线粒体功能对于自发性突触事件的增加是必要的，因为线粒体功能的抑制消除了增加。BCL-xL转染增加了线粒体的数量，并部分通过其对GTP酶DRP-1的影响改善了线粒体在突触位点的定位。相反，内源性BCL-xL的减少会降低突触发生，而不会减弱细胞活力。BCL-xL不仅将新分裂的线粒体引导到突触位点，还增强了胞质溶胶内ATP的可用性，同时降低了穿过神经元膜的氧通量。因此，除了防止神经元中的细胞死亡之外，我们认为BCL-xL增强线粒体效率并改变线粒体位置，从而可能产生突触成熟。