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

Overview

Journal Neurochem Res

Specialties Chemistry
Neurology

Date 2021 Feb 13

PMID 33580369

Citations 16

Authors

Yingying Xu

Ling Cheng

Jing Sun

Fan Li

Xiangtian Liu

Yan Wei

Min Han

Zhengyu Zhu

Jianzhong Bi

Chao Lai

Yun Wang

Affiliations

Soon will be listed here.

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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