SARS-CoV-2 altered mitochondrial DNA methylation in Indian COVID-19 patients

The COVID-19 disease, caused by Severe Acute Respiratory Syndrome Coronavirus 2, proved to be a global pandemic with effect on mitochondrial functions. Mitochondrial genetics plays an essential role in disease severity. We identified differential methylation patterns in mitochondrial DNA and nuclear encoded mitochondrial genes in Indian COVID-19 patients through bisulphite sequencing. The study groups included severe deceased, recovered and healthy individuals. Differentially methylated regions (DMR) were obtained. Based on DMRs, differentially methylated genes (DMGs) having methylation in promoter regions were identified. A significantly higher amount of differential methylation is observed in the promoter regions of the genes indicating alterations in gene regulation. Gene ontological and pathway analysis was conducted. In gene ontology analysis, biological processes, cellular components, and molecular functions repeatedly revealed terms associated with the mitochondrial complex assembly (I and IV) and oxidative phosphorylation. KEGG pathway analysis showed that the highest number of DMGs were associated with metabolic pathways, thermogenesis, diabetic cardiomyopathy and oxidative phosphorylation. Significantly elevated levels of mitochondrial dynamics proteins DNM1L, TOMM20 and TOMM22 were found in COVID-19 patients. In conclusion, the mitochondria related DNA methylation could affect the expression of genes involved in the progression of COVID-19 contributing to mitochondrial dysfunction in the disease.