Neuroendocrine Coordination of Mitochondrial Stress Signaling and Proteostasis.
Neuroendocrine Coordination of Mitochondrial Stress Signaling and Proteostasis.
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DOI：
10.1016/j.cell.2016.08.042
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发表时间：
2016-09-08
期刊：
影响因子：
64.5
通讯作者：
Dillin A
中科院分区：
文献类型：
--
作者：
Berendzen KM;Durieux J;Shao LW;Tian Y;Kim HE;Wolff S;Liu Y;Dillin A
在神经退行性疾病中，聚集体和错误折叠蛋白的毒性积累通常伴随着外周代谢的广泛变化，即使在不存在聚集体蛋白的细胞中也是如此。中枢神经系统对蛋白毒性应激产生远端反应的机制尚不清楚。我们假设神经元应激的内分泌通讯在与蛋白质毒性疾病状态相关的线粒体稳态变化中起着致病作用。我们发现秀丽隐杆线虫神经元中表达的一种易于聚集的蛋白与线粒体结合，引发线粒体特异性未折叠蛋白反应（UPRmt）的全球诱导，影响整个动物的生理。重要的是，密集的核心囊泡释放和神经递质血清素的分泌是信号传播所必需的。总的来说，这些数据表明，在神经系统中蛋白质折叠压力的反应中，营养传感网络的控制允许线粒体之间的细胞间通信。神经系统中的线粒体压力是如何向其他组织发出信号的？
During neurodegenerative disease, the toxic accumulation of aggregates and misfolded proteins is often accompanied with widespread changes in peripheral metabolism, even in cells in which the aggregating protein is not present. The mechanism by which the central nervous system elicits a distal reaction to proteotoxic stress remains unknown. We hypothesized that the endocrine communication of neuronal stress plays a causative role in the changes in mitochondrial homeostasis associated with proteotoxic disease states. We find that an aggregation-prone protein expressed in the neurons of C. elegans binds to mitochondria, eliciting a global induction of a mitochondrial-specific unfolded protein response (UPRmt), affecting whole-animal physiology. Importantly, dense core vesicle release and secretion of the neurotransmitter serotonin is required for the signal’s propagation. Collectively, these data suggest the commandeering of a nutrient sensing network to allow for cell-to-cell communication between mitochondria in response to protein folding stress in the nervous system. How is mitochondrial stress in the nervous system signaled to other tissues?
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