Drp1-mediated mitochondrial fission contributes to mitophagy in paraquat-induced neuronal cell damage
Drp1-mediated mitochondrial fission contributes to mitophagy in paraquat-induced neuronal cell damage
复制标题
Drp1 介导的线粒体裂变导致百草枯诱导的神经细胞损伤中的线粒体自噬
DOI：
10.1016/j.envpol.2020.116413
复制
发表时间：
2021-03-01
影响因子：
8.9
通讯作者：
Li, Huangyuan
中科院分区：
文献类型：
--
作者：
Chen, Nengzhou;Guo, Zhenkun;Li, Huangyuan
百草枯具有优良的除草效果，是目前世界上应用最广泛的除草剂之一。越来越多的证据表明，长期暴露于PQ可以显著增加帕金森病（PD）的风险。然而，潜在的分子机制尚未完全了解。因此，我们研究了活性氧（ROS）和动力蛋白相关蛋白1 （DRP1）在pq诱导的线粒体自噬中的潜在作用，旨在阐述pq引发神经毒性的可能分子机制。结果显示，在100、200、300 μ M PQ浓度下，神经元细胞ROS增加，线粒体膜电位降低，自噬途径在100 μ M浓度下激活。此外，暴露于300 μ M PQ 24 h的神经元出现了过度的线粒体自噬。然后发现ros介导的线粒体分裂有助于PQ诱导过度的线粒体自噬。此外，上述所有变化都被mdivi-1显著改善。因此，我们的研究结果提供了一种新的神经毒性机制，并揭示了drp1 -线粒体分裂途径作为治疗pq诱导的过度线粒体自噬的潜在靶点，可作为预防和治疗帕金森病的替代靶点。由于有害物质在食物链中传播和富集，环境百草枯的毒性作用不可忽视，需要更多的研究。(C) 2021 Elsevier Ltd版权所有。
Paraquat (PQ) is one of the most widely used herbicides in the world due to its excellent weed control effects. Accumulating evidence has revealed that long-term exposure to PQ can significantly increase the risk of Parkinson's disease (PD). However, the underlying molecular mechanisms are yet to be fully understood. Hence, we investigated the potential role of reactive oxygen species (ROS) and dynamin-related protein 1 (DRP1) in PQ-induced mitophagy, aiming to elaborate on possible molecular mechanisms involved in PQ-triggered neurotoxicity. Our results showed that ROS were increased, mitochondrial membrane potential was decreased at 100, 200, and 300 mu M PQ concentrations, and autophagy pathways were activated at a concentration of 100 mu M in neuronal cells. In addition, excessive mitophagy was observed in neurons exposed to 300 mu M PQ for 24 h. Then, ROS-mediated mitochondrial fission was found to contribute to PQ-induced excessive mitophagy. Moreover, all aforementioned changes were significantly ameliorated by mdivi-1. Thus, our findings provide a novel neurotoxic mechanism and reveal the DRP1-mitochondrial fission pathway as a potential target for treatments of PQ-induced excessive mitophagy, serving as an alternative target for the prevention and treatment of Parkinson's disease. Because harmful substances are transmitted and enriched in the food chain, the toxic effect of environmental paraquat is nonnegligible, and more investigations are needed. (C) 2021 Elsevier Ltd. All rights reserved.