Integrated mitoepigenetic signalling mechanisms associated with airborne particulate matter exposure: A cross-sectional pilot study

Abstract

Airborne particulate matter (PM) is known to be associated with various chronic human ailments, however, precise underlying molecular mechanisms remains elusive. Based on the place of residence and amount of PM exposure, the study groups were divided into high-risk group and low-risk group. Different parameters related to oxidative DNA damage and repair, integrated stress response, mito-nuclear crosstalk, mitochondrial biogenesis, functioning and epigenetic machinery were assessed. The results of our pilot study showed that in comparison to the low-risk group, the levels of mitochondrial stress and oxidative DNA damage were significantly higher in the high-risk group. In addition, the upregulated expression levels of OMA1, DELE1, and HRI genes in the high-risk group confirmed the onset of an integrated stress response. These disturbances in the mitochondrial genome were further found to be associated with the vital processes of mitochondrial biogenesis. The high-risk group reported significant alterations in the mtDNA copy number and expression of mitochondrial fission and fusion genes. Importantly, we also observed higher expression levels of mitochondrial transcription factor TFAM, a key regulator of mtDNA replication and transcription in the high-risk group. Moreover, these changes were accompanied by the disturbances in the expression of TET genes and levels of mtDNA methylation. This impaired mtDNA methylation profile further correlated with the disturbed activity of electron chain complexes and expression of the mitochondria function genes in the high-risk group. Altogether, our observations provide vital molecular insights of the integrated mitoepigenetic signalling network in the airborne PM exposed individuals, hitherto unreported.