Mitochondrial Ultrastructure Is Coupled to Synaptic Performance at Axonal Release Sites.

Mitochondrial Ultrastructure Is Coupled to Synaptic Performance at Axonal Release Sites.
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DOI:
10.1523/eneuro.0390-17.2018
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发表时间:
2018-01
期刊:
影响因子:
3.4
通讯作者:
Dénes Á
Dénes Á
中科院分区:
医学3区
文献类型:
--
作者:
Cserép C;Pósfai B;Schwarcz AD;Dénes Á

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神经元中的线粒体功能与最终决定神经元性能的代谢和信号传导机制紧密相关。这些细胞器的亚细胞分布是动态调节的,因为它们被定向到轴突释放位点的需求,但线粒体内部的超微结构和分子特性是否会反映突触特异性方式的实际性能要求,仍有待建立。在这里,我们研究了小鼠和人类GABA能和谷氨酸能轴突中突触前线粒体的超微结构特征。使用电子断层扫描和超分辨率显微镜,我们发现,这些功能被耦合到突触强度:线粒体在具有高突触活性的终扣表现出超微结构优化的高速率代谢,并包含更高水平的呼吸链蛋白质细胞色素C(CytC)比线粒体在较低的活动终扣。线粒体超微结构,分子指纹和突触性能之间的强,细胞类型无关的相关性表明,突触活动的变化可能会触发突触前线粒体的超微结构可塑性,可能会调整其性能的实际代谢需求。
Mitochondrial function in neurons is tightly linked with metabolic and signaling mechanisms that ultimately determine neuronal performance. The subcellular distribution of these organelles is dynamically regulated as they are directed to axonal release sites on demand, but whether mitochondrial internal ultrastructure and molecular properties would reflect the actual performance requirements in a synapse-specific manner, remains to be established. Here, we examined performance-determining ultrastructural features of presynaptic mitochondria in GABAergic and glutamatergic axons of mice and human. Using electron-tomography and super-resolution microscopy we found, that these features were coupled to synaptic strength: mitochondria in boutons with high synaptic activity exhibited an ultrastructure optimized for high rate metabolism and contained higher levels of the respiratory chain protein cytochrome-c (CytC) than mitochondria in boutons with lower activity. The strong, cell type-independent correlation between mitochondrial ultrastructure, molecular fingerprints and synaptic performance suggests that changes in synaptic activity could trigger ultrastructural plasticity of presynaptic mitochondria, likely to adjust their performance to the actual metabolic demand.