Hypermethylation of Mitochondrial Cytochrome b and Cytochrome c Oxidase II Genes with Decreased Mitochondrial DNA Copy Numbers in the APP/PS1 Transgenic Mouse Model of Alzheimer’s Disease

Neurochemical Research volume 46, pages564–572(2021)Cite this article

Abstract

Alzheimer’s disease (AD) is the most common cause of dementia. Increasing evidence shows that mitochondrial DNA (mtDNA) methylation plays an essential role in many diseases related to mitochondrial dysfunction. Since mitochondrial impairment is a key feature of AD, mtDNA methylation may also contribute to AD, but few studies have addressed this issue. Methylation changes of the mitochondrial cytochrome b (CYTB) and cytochrome c oxidase II (COX II) genes in AD have not been reported. We analyzed mtDNA methylation changes of the CYTB and COX II genes in an APP/PS1 transgenic mouse model of AD using pyrosequencing. We examined mtDNA copy numbers and the levels of expression by quantitative real-time PCR. Average methylation levels of different CpG sites were ≤ 4.0%. Methylated mtDNA accounted for only a small part of the total mtDNA. We also observed hypermethylation of mitochondrial CYTB and COX II genes with decreased mtDNA copy numbers and expression in the hippocampi of APP/PS1 transgenic mice. mtDNA methylation may play an important role in AD pathology, which may open a new window for AD therapy.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 81870848) and the Key Research and Development Program of Shandong Province (Grant No. 2017GSF218046).

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Affiliations

  1. Department of Neurology Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247th of Beiyuan Rd., Jinan, Shandong, China

    Yingying Xu, Ling Cheng, Fan Li, Xiangtian Liu, Yan Wei, Zhengyu Zhu, Jianzhong Bi, Chao Lai & Yun Wang

  2. Department of Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247th of Beiyuan Rd., Jinan, Shandong, China

    Jing Sun

  3. Department of General Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, 247th of Beiyuan Rd., Jinan, Shandong, China

    Min Han

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  1. Yingying Xu
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  2. Ling Cheng
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  3. Jing Sun
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  4. Fan Li
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  6. Yan Wei
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Correspondence to Chao Lai or Yun Wang.

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Xu, Y., Cheng, L., Sun, J. et al. Hypermethylation of Mitochondrial Cytochrome b and Cytochrome c Oxidase II Genes with Decreased Mitochondrial DNA Copy Numbers in the APP/PS1 Transgenic Mouse Model of Alzheimer’s Disease. Neurochem Res 46, 564–572 (2021). https://doi.org/10.1007/s11064-020-03192-y

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Keywords

  • Alzheimer’s disease
  • Mitoepigenetics
  • Mitochondrial DNA methylation
  • Electron transport chain
  • Pyrosequencing