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

Area of Science:

• Environmental Health
• Mitochondrial Biology
• Toxicology

Background:

• Mitochondria are susceptible to environmental toxicants due to limited repair capabilities.
• Particulate matter (PM₁₀) exposure is a significant environmental stressor.
• Understanding mitochondrial responses to PM₁₀ is crucial for public health.

Purpose of the Study:

• To investigate the effects of short- and medium-term PM₁₀ exposure on mitochondrial gene expression and pathways.
• To identify sex-specific differences in mitochondrial responses to air pollution.
• To explore potential compensatory mechanisms in energy production.

Main Methods:

• Whole genome gene expression analysis in peripheral blood of 98 adults.
• Linear regression analyses stratified by sex and adjusted for covariates.
• Overrepresentation analyses to identify enriched mitochondrial pathways and gene ontology sets.
• Validation of key mitochondrial genes and mitochondrial DNA (mtDNA) content in an independent cohort.

Main Results:

• Short-term PM₁₀ exposure in women was linked to pathways involved in mitochondrial genome maintenance and apoptosis.
• Medium-term PM₁₀ exposure in women was associated with the electron transport chain (ETC).
• Medium-term PM₁₀ exposure in men showed associations with the Tri Carbonic Acid cycle.
• Validation confirmed alterations in ETC genes (e.g., UQCRH, COX7C) and mitochondrial genome maintenance genes (e.g., POLG) in women.

Conclusions:

• Mitochondrial genes and pathways are associated with particulate air pollution exposure.
• Upregulation of energy-producing pathways may be a compensatory response to PM-induced mitochondrial damage.
• Sex-specific responses highlight the need for tailored environmental health strategies.