The scientific evidence that air pollution may be a risk factor for metabolic disease has been steadily increasing, yet the biological mechanisms driving such associations are not well understood. One of the key players in metabolism are the mitochondria; in fact, dysfunctional mitochondria have been implicated in a variety of diseases including metabolic disease. Mitochondrial DNA (mtDNA) is also sensitive to damage by exogenous reactive oxygen species. Environmental pollutants, such as traffic-related air pollution (TRP), known to generate oxidative stress, have been associated with various forms of mitochondrial damage. Genetic and epigenetic alterations in the mitochondrial genome may also play pivotal roles in disease susceptibility. Polymorphisms in the mtDNA sequence, specifically certain haplogroups, are known to modify the relationship between TRP exposure and systemic biomarkers of oxidative stress-induced inflammation as well as black carbon and cognitive impairment. Mitochondria also contain the machinery required to epigenetically modify mtDNA expression, suggesting that epigenetic modifications may also affect disease risk. In our own preliminary study, prenatal exposure to non-freeway NOx and Benzo[a]pyrene was associated with altered levels of mtDNA methylation. However, the evidence regarding whether mitochondrial epigenetic marks are sensitive to pro-oxidant environmental exposures, and what time periods in the lifespan are most susceptible, is very limited. Given the important role for mitochondria in metabolism and the suggested associations between air pollutants and metabolic disorders in childhood, w e hypothesize that prenatal exposure to air pollutants may cause mitochondrial DNA damage and alteration to newborn mtDNA in response to exposure-induced systemic oxidation, which may affect early life health outcomes related to metabolic disease. We further hypothesize the mtDNA haplogroups may alter susceptibility to the health effects of air pollutants. We will investigate these hypotheses in detail in a cohort of 300 mother infant pairs recruited at the time of delivery at LAC +USC County hospital.
Mitochondria, which play a key role on cellular metabolism, may be an under-appreciated driving force behind observations of increased risk of metabolic disease from high air pollution exposures. Mitochondrial DNA (mtDNA) is also sensitive to damage by air pollution and contains the epigenetic machinery required to epigenetically modify mtDNA expression; yet little is known about the susceptibility of mitochondrial epigenetic marks to pro-oxidant environmental exposures. Given the important role for mitochondria in metabolism and the suggested associations between air pollutants and metabolic disorders in childhood, we hypothesize that prenatal exposure to air pollutants may cause mitochondrial DNA damage and alteration to newborn mtDNA in response to exposure-induced systemic oxidation, which may vary by haplogroup and which may affect early life health outcomes related to metabolic disease.
| Alderete, T L; Song, A Y; Bastain, T et al. (2018) Prenatal traffic-related air pollution exposures, cord blood adipokines and infant weight. Pediatr Obes 13:348-356 |
| Breton, Carrie V; Marsit, Carmen J; Faustman, Elaine et al. (2017) Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children's Environmental Health Studies: The Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. Environ Health Perspect 125:511-526 |
