College of Life Science & Biotechnology Technology, Heilongjiang Bayi Agricultural University, 163319, Daqing, China.
Primate Resources Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 351-33 Neongme-gil, Ibam-myeon, 56216, Jeongeup-si, Jeonbuk, Republic of Korea.
Cell Commun Signal. 2024 Apr 18;22(1):231. doi: 10.1186/s12964-024-01613-x.
Neurodegenerative diseases are increasingly recognized for their association with oxidative stress, which leads to progressive dysfunction and loss of neurons, manifesting in cognitive and motor impairments. This study aimed to elucidate the neuroprotective role of peroxiredoxin II (Prx II) in counteracting oxidative stress-induced mitochondrial damage, a key pathological feature of neurodegeneration.
We investigated the impact of Prx II deficiency on endoplasmic reticulum stress and mitochondrial dysfunction using HT22 cell models with knocked down and overexpressed Prx II. We observed alcohol-treated HT22 cells using transmission electron microscopy and monitored changes in the length of mitochondria-associated endoplasmic reticulum membranes and their contact with endoplasmic reticulum mitochondria contact sites (EMCSs). Additionally, RNA sequencing and bioinformatic analysis were conducted to identify the role of Prx II in regulating mitochondrial transport and the formation of EMCSs.
Our results indicated that Prx II preserves mitochondrial integrity by facilitating the formation of EMCSs, which are essential for maintaining mitochondrial Ca homeostasis and preventing mitochondria-dependent apoptosis. Further, we identified a novel regulatory axis involving Prx II, the transcription factor ATF3, and miR-181b-5p, which collectively modulate the expression of Armcx3, a protein implicated in mitochondrial transport. Our findings underscore the significance of Prx II in protecting neuronal cells from alcohol-induced oxidative damage and suggest that modulating the Prx II-ATF3-miR-181b-5p pathway may offer a promising therapeutic strategy against neurodegenerative diseases.
This study not only expands our understanding of the cytoprotective mechanisms of Prx II but also offers necessary data for developing targeted interventions to bolster mitochondrial resilience in neurodegenerative conditions.
神经退行性疾病越来越被认为与氧化应激有关，氧化应激导致神经元逐渐功能障碍和丧失，表现为认知和运动障碍。本研究旨在阐明过氧化物酶 II（Prx II）在对抗氧化应激诱导的线粒体损伤中的神经保护作用，这是神经退行性变的一个关键病理特征。
我们使用敲低和过表达 Prx II 的 HT22 细胞模型，研究了 Prx II 缺乏对内质网应激和线粒体功能障碍的影响。我们使用透射电子显微镜观察了酒精处理的 HT22 细胞，并监测了线粒体相关内质网膜的长度变化及其与内质网线粒体接触位点（EMCSs）的接触情况。此外，进行了 RNA 测序和生物信息学分析，以确定 Prx II 在调节线粒体运输和 EMCSs 形成中的作用。
我们的结果表明，Prx II 通过促进 EMCSs 的形成来保护线粒体的完整性，这对于维持线粒体 Ca 稳态和防止线粒体依赖性细胞凋亡至关重要。此外，我们确定了一个涉及 Prx II、转录因子 ATF3 和 miR-181b-5p 的新调节轴，它们共同调节 Armcx3 的表达，Armcx3 是一种参与线粒体运输的蛋白质。我们的研究结果强调了 Prx II 在保护神经元细胞免受酒精诱导的氧化损伤中的重要性，并表明调节 Prx II-ATF3-miR-181b-5p 途径可能为神经退行性疾病提供一种有前途的治疗策略。
本研究不仅扩展了我们对 Prx II 细胞保护机制的理解，还为开发靶向干预措施提供了必要的数据，以增强神经退行性疾病条件下的线粒体弹性。
