Bioenergetic analysis of isolated cerebrocortical nerve terminals on a microgram scale: spare respiratory capacity and stochastic mitochondrial failure.
Bioenergetic analysis of isolated cerebrocortical nerve terminals on a microgram scale: spare respiratory capacity and stochastic mitochondrial failure.
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DOI：
10.1111/j.1471-4159.2009.06055.x
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发表时间：
2009-05
影响因子：
4.7
通讯作者：
Nicholls DG
中科院分区：
文献类型：
--
作者：
Choi SW;Gerencser AA;Nicholls DG
突触前神经末梢（突触体）需要ATP用于神经递质的胞吐和恢复以及离子稳态，因此大量配备有线粒体。突触前线粒体功能障碍与多种神经退行性疾病有关，尽管术语"功能障碍"没有精确的定义。在这项研究中，我们测试的假设，通过复合物I和II在突触体中的电子传递的部分限制，以模仿可能的缺陷与帕金森氏病和亨廷顿病分别，敏感的个人终端线粒体去极化的条件下，增强质子电流的利用率，即使这些压力是在呼吸能力的突触体时，平均在整个人口。我们结合联合收割机两种新的技术，首先使用一种新的基于板的呼吸和糖酵解测定，只需要微克数量的突触体蛋白的修改，其次开发一种改进的方法荧光成像和统计分析的单个突触体。条件被定义为最佳的基板供应到原位线粒体内的小鼠皮层突触体，离子循环和动作电位发射在质膜的能量需求另外确定。
Presynaptic nerve terminals (synaptosomes) require ATP for neurotransmitter exocytosis and recovery and for ionic homeostasis, and are consequently abundantly furnished with mitochondria. Presynaptic mitochondrial dysfunction is implicated in a variety of neurodegenerative disorders, although there is no precise definition of the term ‘dysfunction’. In this study we test the hypothesis that partial restriction of electron transport through Complexes I and II in synaptosomes to mimic possible defects associated with Parkinson's and Huntington's diseases respectively, sensitizes individual terminals to mitochondrial depolarization under conditions of enhanced proton current utilization, even though these stresses are within the respiratory capacity of the synaptosomes when averaged over the entire population. We combine two novel techniques, firstly using a modification of a novel plate-based respiration and glycolysis assay that requires only microgram quantities of synaptosomal protein, and secondly developing an improved method for fluorescent imaging and statistical analysis of single synaptosomes. Conditions are defined for optimal substrate supply to the in situ mitochondria within mouse cerebrocortical synaptosomes, and the energetic demands of ion cycling and action potential firing at the plasma membrane are additionally determined.
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影响因子：
3
作者：
Bambrick, Linda L.;Chandrasekaran, Krish;Fiskum, Gary
通讯作者：
Fiskum, Gary
影响因子：
3.3
作者：
Nayak, SV;Rondé, P;Nichols, RA
通讯作者：
Nichols, RA
影响因子：
14.8
作者：
Dunkley, Peter R.;Jarvie, Paula E.;Robinson, Phillip J.
通讯作者：
Robinson, Phillip J.
影响因子：
4.1
作者：
NICHOLLS, DG;SCOTT, ID
通讯作者：
SCOTT, ID
影响因子：
6.1
作者：
Betarbet, R;Canet-Aviles, RA;Greenamyre, JT
通讯作者：
Greenamyre, JT