Stavrovskaya Irina, Morin Bethany Kristi, Madamba Stephen, Alexander Cliyahnelle, Romano Alexis, Alam Samia, Pavlov Lucas, Mitaishvili Erna, Peixoto Pablo M
Baruch College and CUNY Graduate Center, 1 Baruch Way, New York, NY, 10010, USA.
Baruch College and CUNY Graduate Center, 1 Baruch Way, New York, NY, 10010, USA.
Redox Biol. 2025 Feb;79:103474. doi: 10.1016/j.redox.2024.103474. Epub 2024 Dec 22.
The elevated emission of reactive oxygen species (ROS) from presynaptic mitochondria is well-documented in several inflammatory and neurodegenerative diseases. However, the potential role of mitochondrial ROS in presynaptic function and plasticity remains largely understudied beyond the context of disease. Here, we investigated this potential ROS role in presynaptic function and short-term plasticity by combining optogenetics, whole cell electrophysiological recordings, and live confocal imaging using a well-established protocol for induction and measurement of synaptic potentiation in Drosophila melanogaster neuromuscular junctions (NMJ). Optogenetic induction of ROS emission from presynaptic motorneuron mitochondria expressing mitokiller red (mK) resulted in synaptic potentiation, evidenced by an increase in the frequency of spontaneous mini excitatory junction potentials. Notably, this effect was not observed in flies co-expressing catalase, a cytosolic hydrogen peroxide (HO) scavenging enzyme. Moreover, the increase in electrical activity did not coincide with synaptic structural changes. The absence of Wnt1/Wg release from synaptic boutons suggested involvement of alternative or non-canonical signaling pathway(s). However, in existing boutons we observed an increase in the active zone (AZ) marker Brp/Erc1, which serves as docking site for the neurotransmitter vesicle release pool. We propose the involvement of putative redox switches in AZ components as the molecular target of mitochondrial HO. These findings establish a novel framework for understanding the signaling role of mROS in presynaptic structural and functional plasticity, providing insights into redox-based mechanisms of neuronal communication.
在几种炎症性和神经退行性疾病中，突触前线粒体活性氧（ROS）的升高排放已有充分记录。然而，除了疾病背景外，线粒体ROS在突触前功能和可塑性中的潜在作用仍 largely understudied。在这里，我们通过结合光遗传学、全细胞电生理记录和实时共聚焦成像，使用一种成熟的方案来诱导和测量果蝇神经肌肉接头（NMJ）中的突触增强，研究了这种潜在的ROS在突触前功能和短期可塑性中的作用。从表达mitokiller red（mK）的突触前运动神经元线粒体光遗传学诱导ROS排放导致突触增强，这通过自发微小兴奋性接头电位频率的增加得到证明。值得注意的是，在共表达过氧化氢酶（一种胞质过氧化氢（HO）清除酶）的果蝇中未观察到这种效应。此外，电活动的增加与突触结构变化不一致。突触小体中Wnt1/Wg释放的缺失表明涉及替代或非经典信号通路。然而，在现有的突触小体中，我们观察到活性区（AZ）标记物Brp/Erc1增加，它作为神经递质囊泡释放池的停靠位点。我们提出假定的氧化还原开关参与AZ成分作为线粒体HO的分子靶点。这些发现建立了一个新的框架，用于理解mROS在突触前结构和功能可塑性中的信号作用，为基于氧化还原的神经元通讯机制提供了见解。
