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

Mitochondrion. 2019 May;46:22-29. doi: 10.1016/j.mito.2019.04.001. Epub 2019 Apr 10.

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.

Keywords: Air pollution; DNA methylation; Epigenetics; Mitochondria; Particulate matter; Traffic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Air Pollutants / toxicity*
  • Animals
  • Cells, Cultured
  • Cohort Studies
  • DNA Methylation*
  • DNA, Mitochondrial / metabolism*
  • Environmental Exposure
  • Female
  • Gene Expression
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mice, Inbred C57BL
  • Mitochondria / drug effects*
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism*
  • Models, Animal
  • Pregnancy
  • Young Adult

Substances

  • Air Pollutants
  • DNA, Mitochondrial
  • Mitochondrial Proteins