Transcriptome-wide analyses indicate mitochondrial responses to particulate air pollution exposure

Ellen Winckelmans,Karen Vrijens,Elly Den Hond,Greet Schoeters,Jos Kleinjans,Tim S Nawrot,Hans Reynders,Maria Tsamou,Wouter Lefebvre,Michelle Plusquin,Willy Baeyens,Charlotte Vanpoucke,Theo M De Kok,Nicolas Van Larebeke,Martien Peusens

doi:10.1186/s12940-017-0292-7

Abstract

BackgroundDue to their lack of repair capacity mitochondria are critical targets for environmental toxicants. We studied genes and pathways reflecting mitochondrial responses to short- and medium-term PM10 exposure.MethodsWhole genome gene expression was measured in peripheral blood of 98 adults (49% women). We performed linear regression analyses stratified by sex and adjusted for individual and temporal characteristics to investigate alterations in gene expression induced by short-term (week before blood sampling) and medium-term (month before blood sampling) PM10 exposure. Overrepresentation analyses (ConsensusPathDB) were performed to identify enriched mitochondrial associated pathways and gene ontology sets. Thirteen Human MitoCarta genes were measured by means of quantitative real-time polymerase chain reaction (qPCR) along with mitochondrial DNA (mtDNA) content in an independent validation cohort (n = 169, 55.6% women).ResultsOverrepresentation analyses revealed significant pathways (p-value <0.05) related to mitochondrial genome maintenance and apoptosis for short-term exposure and to the electron transport chain (ETC) for medium-term exposure in women. For men, medium-term PM10 exposure was associated with the Tri Carbonic Acid cycle. In an independent study population, we validated several ETC genes, including UQCRH and COX7C (q-value <0.05), and some genes crucial for the maintenance of the mitochondrial genome, including LONP1 (q-value: 0.07) and POLG (q-value: 0.04) in women.ConclusionsIn this exploratory study, we identified mitochondrial genes and pathways associated with particulate air pollution indicating upregulation of energy producing pathways as a potential mechanism to compensate for PM-induced mitochondrial damage.

Highlights

Due to their lack of repair capacity mitochondria are critical targets for environmental toxicants
Mitochondria are cellular organelles specialized in energy production and produce the majority of intracellular reactive oxygen species (ROS), which are continually generated as toxic by-products by the electron transport chain (ETC)
We investigated associations between PM10 exposure and expression of 1064 genes listed in the “Human MitoCarta2.0” inventory [11, 12] which are known to encode proteins with mitochondrial localization

Summary

Introduction

Due to their lack of repair capacity mitochondria are critical targets for environmental toxicants. We studied genes and pathways reflecting mitochondrial responses to short- and medium-term PM10 exposure. Winckelmans et al Environmental Health (2017) 16:87 peroxidation by ROS, resulting in reactive aldehydes which can further damage mitochondrial structures [3, 5]. A pathway analysis was performed on genome wide transcriptome data to investigate whether mitochondrial pathways are highly affected by air pollution exposure. This hypothesis-generating approach identified sex-specific mitochondrial related genes associated with short- and medium-term PM10 exposure that were analysed further in a validation study by means of real-time quantitative PCR (qRT-PCR)

Methods

Results

Discussion

Conclusion