2. Academic Validation
  3. MitoQ alleviates prion-induced neurodegeneration by modulating DRP1- and OPA1-mediated mitochondrial dynamics

MitoQ alleviates prion-induced neurodegeneration by modulating DRP1- and OPA1-mediated mitochondrial dynamics

  • Free Radic Biol Med. 2025 Oct:238:582-594. doi: 10.1016/j.freeradbiomed.2025.07.017.
Wei Wu 1,  Xixi Zhang 2,  Jia Xing 3,  Siyu Kong 4,  Mingyue Jiang 5,  Meiyi Zhou 2,  Yi Liao 6,  Baojian Liao 7,  Ning Ma 8
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Guangzhou, 511436, China; Guangzhou National Laboratory, Guangzhou, 510005, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health, Guangdong Laboratory), Guangzhou, 510005, China; The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, China. Electronic address: wu_wei@gzlab.ac.cn.
  • 2 School of Basic Medical Sciences, Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Guangzhou, 511436, China; Guangzhou National Laboratory, Guangzhou, 510005, China.
  • 3 Guangdong Environmental Protection Key Laboratory of Microbiology and Ecological Safety, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, China.
  • 4 Department of Cardiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China.
  • 5 School of Basic Medical Sciences, Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Guangzhou, 511436, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health, Guangdong Laboratory), Guangzhou, 510005, China; Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
  • 6 College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu, 610041, China.
  • 7 School of Basic Medical Sciences, Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Guangzhou, 511436, China; Guangzhou National Laboratory, Guangzhou, 510005, China; The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, China. Electronic address: liaobaojian@gzhmu.edu.cn.
  • 8 School of Basic Medical Sciences, Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Guangzhou, 511436, China; Guangzhou National Laboratory, Guangzhou, 510005, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health, Guangdong Laboratory), Guangzhou, 510005, China; The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, China. Electronic address: ma_ning@gzlab.ac.cn.
PMID: 40651617 DOI: 10.1016/j.freeradbiomed.2025.07.017
Abstract

Prion diseases are a group of fatal neurodegenerative disorders with no effective treatments. MitoQ, a mitochondria-targeted antioxidant, has shown promise in treating mitochondrial redox-related diseases; however, its role in prion diseases remains unclear. In this study, we demonstrate that MitoQ significantly alleviates PrP106-126-induced oxidative stress, mitochondrial dysfunction, and Apoptosis in mouse neuroblastoma N2a cells. Specifically, MitoQ reduces intracellular and mitochondrial Reactive Oxygen Species (ROS) accumulation, enhances total antioxidant capacity (T-AOC) and the glutathione (GSH)/oxidized glutathione (GSSG) ratio, restores oxygen consumption rate (OCR), mitochondrial membrane potential (MMP) and intracellular ATP levels, and prevents cytochrome c release and Caspase 3 activation. Mechanistically, MitoQ downregulates dynamin-related protein 1 (DRP1) phosphorylation at Ser616 and reduces mitochondrial DRP1 accumulation, while upregulating optic atrophy 1 (OPA1), thereby improving the mitochondrial dynamics imbalance induced by PrP106-126. Notably, DRP1 overexpression or OPA1 knockdown abolishes these protective effects, resulting in persistent oxidative stress, mitochondrial dysfunction, and Apoptosis. These findings suggest that MitoQ alleviates prion-induced neurodegeneration by modulating DRP1- and OPA1-mediated mitochondrial dynamics, highlighting its therapeutic potential in prion diseases.

Keywords

DRP1 and OPA1; MitoQ; Mitochondrial dynamics; Mitochondrial dysfunction; Oxidative stress; Prion diseases.

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