Mitochondrial ROS signaling during synaptic potentiation

Mitochondrial ROS signaling during synaptic potentiation
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突触增强过程中线粒体 ROS 信号传导

DOI:
10.1016/j.bpj.2021.11.223
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发表时间:
2022
影响因子:
3.4
通讯作者:
Peixoto, Pablo M.
Peixoto, Pablo M.
中科院分区:
生物学3区
文献类型:
--
作者:
Stavrovskaya, Irina;Mitaishvilli, Erna;Morin, Bethany Kristi;Walls, Aria;Terry, Grace;Peixoto, Pablo M.

文献摘要

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突触前线粒体活性氧物种(ROS)的加速释放是包括肌萎缩侧索硬化症在内的几种神经退行性疾病的一个被广泛研究的标志。在病理学之外,线粒体ROS在突触前功能和可塑性中的潜在生理作用仍未得到很大程度的研究。在这里,我们通过结合光遗传技术、电生理记录、共聚焦显微镜和成熟的诱导和测量果蝇神经肌肉标本中突触增强的方法来研究这种潜在的作用。我们观察到自发微型兴奋性连接电位(MEJP)的预期增加,同时通过共聚焦成像观察到表达roGFP2-Orp1的突触前运动神经元线粒体的ROS发射暂时增加。此外,在光遗传诱导表达有丝分裂杀手红的突触前线粒体释放ROS后,我们能够复制这种mEJP频率的增加。这些初步但令人兴奋的结果可能表明线粒体ROS信号在突触增强中的潜在作用。进一步的研究将探讨这一作用,以及线粒体ROS在果蝇神经肌肉接头突触前结构中的潜在信号靶点。
Exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a well-studied hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis. Outside the context of pathology, the potential physiological role of mitochondrial ROS in presynaptic function and plasticity remains largely understudied. Here, we investigated this potential role by combining optogenetic techniques, electrophysiological recordings, confocal microscopy, and a well-established protocol for induction and measurement of synaptic potentiation in drosophila neuromuscular preparations. We observed an expected increase in spontaneous miniature excitatory junction potentials (mEJP), accompanied by a temporary increase in ROS emission seen by confocal imaging of presynaptic motor neuron mitochondria expressing roGFP2-Orp1. Furthermore, we were able to replicate this increase in mEJP frequency after optogenetic induction of ROS emission from pre-synaptic mitochondria expressing mito-killer red. These preliminary but exiting results may indicate a potential role of mitochondrial ROS signaling in synaptic potentiation. Further studies will inquire about this role, as well as the potential signaling targets of mitochondrial ROS in the presynaptic structure of drosophila neuromuscular junctions.