Effects of air pollution on mitochondrial function, mitochondrial DNA methylation, and mitochondrial peptide expression

Abstract

Mitochondrial DNA is sensitive to damage by exogenous reactive oxygen sources, including traffic-related air pollution (TRAP). Given the important role for mitochondria in human disease, we hypothesized that prenatal air pollution exposure may be associated with mitochondrial dysfunction and that mitochondrial-derived peptides (MDPs) might protect against these effects. In in vitro studies, 24-hour exposure to nanoparticulate matter (nPM) increased oxidation of mtDNA, decreased mitochondrial consumption rate (OCR), and decreased mtDNAcn in SH-SY5Y cells. Addition of MDPs rescued these effects to varying degrees. Liver tissue taken from C57Bl/6 males exposed for 10 weeks to nPM had lower OCR, lower mtDNAcn and higher MDP levels, similar to in vitro studies. In newborn cord blood, MDP levels were positively associated with prenatal TRAP exposures. Moreover, DNA methylation of two distinct regions of the D-Loop in the mitochondria genome was associated with levels of several MDPs. Our in vitro and in vivo data indicate that TRAP can directly affect mitochondrial respiratory function and mtDNAcn. Treatment of cells with MDPs can counteract TRAP induced-effects. Lastly, we present evidence that suggests MDPs may be regulated in part by mitochondrial DNA methylation in humans.

Mechanisms of lung toxicity induced by biomass burning aerosols

“…MtDNAcn can be used as another indicator of mitochondrial damage because it correlates with the size and number of mitochondria in a cell and may change under different cellular energy demands or different physiological or environmental conditions [33,54]. Recent studies have correlated ambient PM exposure with mitochondrial DNA damage [26,33,54]. Similar to our study, a previous study found that personal exposure to fine PM and benzo [a] pyrene from indoor air pollution reduced MtDNAcns in leukocytes of women from China [55].…”

“…Mitochondria are the major cellular sources of ROS, which are generated as byproducts during normal respiration [26,29,54]. The alterations in ROS levels, the structural changes in the mitochondria observed using TEM and even the reductions in SOD2 levels may suggest that exposure to water-soluble wood tar can lead to mitochondrial damage.…”

“…Toxicological evaluations of ambient PM have been extensively conducted, whereas the toxicology and mechanisms of WSPs and related components have been poorly defined. Recent studies on WSP exposure have suggested that WSPs enhance inflammation and oxidative stress responses [4,[23][24][25][26][27]. The oxidative stress paradigm suggests that low levels of ROS/ oxidative stress can induce antioxidant induction to restore redox homeostasis.…”

Platelet mitochondrial DNA methylation predicts future cardiovascular outcome in adults with overweight and obesity

“…However, the field remains at a nascent stage, with little understanding of the mechanisms underpinning how mtDNA methylation levels may be implicated in the etiology of CVD and/or platelet activation. Recently, it has been demonstrated that mtDNA methylation regulates expression of mitochondrial-derived peptides (MDP) with cytoprotective function [38] suggesting that mtDNA methylation level may be indicative of the overall stress to which the cell is exposed. Additionally, in vitro studies have shown that the presence of 5methylcytosine can alter mitochondrial transcription factor (TFAM) binding and transcription initiation [39].…”

“…It is not known whether these small changes in DNA methylation reflect changes in gene expression. Regardless, they may serve as a biomarker of a cascade of other biological reactions [43][44][45], such as MDP regulation [38].…”