Contributions of Bcl-xL to acute and long term changes in bioenergetics during neuronal plasticity.
Contributions of Bcl-xL to acute and long term changes in bioenergetics during neuronal plasticity.
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DOI：
10.1016/j.bbadis.2013.11.007
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发表时间：
2014-08
影响因子：
6.2
通讯作者：
Jonas, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Jonas, Elizabeth A.
线粒体在神经元活动和突触传递过程中制造和释放代谢物并管理钙，但线粒体功能的长期改变是否有助于神经元可塑性，这是生物体行为模式变化的基础，仍然知之甚少。虽然正常的神经元可塑性可能决定学习，相反，突触强度或神经元兴奋性的持续下降可能预示着神经突回缩和最终的体细胞死亡。抗死亡蛋白如Bcl-xL在细胞死亡刺激期间在神经元索马处提供神经保护，而且似乎增强神经递质释放和突触生长和发育。有人提出，Bcl-xL通过其调节线粒体释放生物能代谢物和钙的能力，其快速改变线粒体定位和形态的能力，以及其与直接改变突触囊泡再循环的蛋白质相互作用的作用来执行这些功能。Bcl-xL在神经元活动期间急性易位到亚细胞膜以实现这些变化。应激刺激后，促凋亡切割的Δ N Bcl-xL（ΔN Bcl-xL）诱导的线粒体离子通道活性导致突触抑制，这由caspase激活调节。在突触刺激减少的生理状态期间，线粒体Bcl-xL的损失和低水平的半胱天冬酶活化在突触功效的长期下降开始之前发生。Bcl-xL改变线粒体膜通透性的程度可能控制突触强度变化的方向。小分子Bcl-xL抑制剂ABT-737在确定Bcl-xL在突触过程中的作用方面是有用的。Bcl-xL对神经元和突触的正常健康至关重要，其功能障碍可能导致神经退行性疾病。
Mitochondria manufacture and release metabolites and manage calcium during neuronal activity and synaptic transmission, but whether long term alterations in mitochondrial function contribute to neuronal plasticity that underlies changes in organism behavior patterns is still poorly understood. Although normal neuronal plasticity may determine learning, in contrast a persistent decline in synaptic strength or neuronal excitability may portend neurite retraction and eventual somatic death. Anti-death proteins such as Bcl-xL provide neuroprotection at the neuronal soma during cell death stimuli, but also appear to enhance neurotransmitter release and synaptic growth and development. It is proposed that Bcl-xL performs these functions through its ability to regulate mitochondrial release of bioenergetic metabolites and calcium, its ability to rapidly alter mitochondrial positioning and morphology as well as its role in interacting with proteins that directly alter synaptic vesicle recycling. Bcl-xL translocates acutely to subcellular membranes during neuronal activity to achieve these changes. After stressful stimuli, pro-apoptotic cleaved delta N Bcl-xL (ΔN Bcl-xL)-induced mitochondrial ion channel activity leads to synaptic depression and this is regulated by caspase activation. During physiological states of decreased synaptic stimulation, loss of mitochondrial Bcl-xL and low level caspase activation occur prior to the onset of long term decline in synaptic efficacy. The degree to which Bcl-xL changes mitochondrial membrane permeability may control the direction of change in synaptic strength. The small molecule Bcl-xL inhibitor ABT-737 has been useful in defining the role of Bcl-xL in synaptic processes. Bcl-xL is crucial to the normal health of neurons and synapses and its malfunction may contribute to neurodegenerative disease.
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影响因子：
21.3
作者：
通讯作者：
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内膜的四十千克蛋白是线粒体钙Uniporter。
影响因子：
64.8
作者：
De Stefani, Diego;Raffaello, Anna;Teardo, Enrico;Szabo, Ildiko;Rizzuto, Rosario
通讯作者：
Rizzuto, Rosario
影响因子：
16
作者：
Cheng, EHYA;Wei, MC;Korsmeyer, SJ
通讯作者：
Korsmeyer, SJ
影响因子：
64.8
作者：
Baughman, Joshua M.;Perocchi, Fabiana;Girgis, Hany S.;Plovanich, Molly;Belcher-Timme, Casey A.;Sancak, Yasemin;Bao, X. Robert;Strittmatter, Laura;Goldberger, Olga;Bogorad, Roman L.;Koteliansky, Victor;Mootha, Vamsi K.
通讯作者：
Mootha, Vamsi K.
NCLX：线粒体钠钙交换器。
影响因子：
5
作者：
Boyman, Liron;Williams, George S. B.;Khananshvili, Daniel;Sekler, Israel;Lederer, W. J.
通讯作者：
Lederer, W. J.