Groundwater arsenic contamination has become a serious global concern due to its adverse effects on human health. Arsenic-induced reactive oxygen species trigger oxidative stress inside mitochondria, which initiate a cascade of events including altered mitochondrial (mt) membrane potential, uncoupling of electron transport chain, and mtDNA damage. A case-control study was conducted to examine the association between arsenic exposure and differences in mtDNA methylation and to assess the downstream consequences. We recruited 221 arsenic-exposed individuals, including 106 individuals with skin lesions (WSL) and 115 subjects without any skin lesions (WOSL) from the Murshidabad district, West Bengal, India. The unexposed group included 101 individuals from the arsenic unexposed area in East Midnapore. We analyzed the status of mtDNA methylation in D-loop region and ND6 gene by methylation-specific PCR. Gene expression was studied by quantitative real-time PCR. Significant hypomethylation in both D-loop and ND6 was observed with a consequent increase in their target gene expression and higher mtDNA copy number in arsenic-exposed populations compared to controls. Further mechanistic insights regarding mitochondrial epigenetic alteration in arsenic exposure will be of critical importance for the prevention of adverse health effects.

地下水砷污染由于其对人体健康的不利影响，已引起全球严重关注。砷诱导的活性氧物质触发线粒体内的氧化应激，从而引发一系列事件，包括线粒体（mt）膜电位改变，电子传输链解偶联和mtDNA损伤。进行了一项病例对照研究，以检查砷暴露与mtDNA甲基化差异之间的关联并评估下游后果。我们从印度西孟加拉邦的Murshidabad地区招募了221名接触砷的个体，其中包括106名有皮肤病变（WSL）的个体和115名没有任何皮肤病变（WOSL）的个体。未暴露人群包括来自东米德纳波勒地区未暴露砷地区的101个人。ND6基因通过甲基化特异性PCR。通过定量实时PCR研究基因表达。与对照组相比，在砷暴露人群中，D环和ND6均出现显着的低甲基化，因此其靶基因表达增加并且mtDNA拷贝数更高。有关砷暴露中线粒体表观遗传学改变的更多机理见解对于预防不良健康影响至关重要。