Environmental Chemical Exposures and Mitochondrial Dysfunction: a Review of Recent Literature

Abstract

Purpose of review: Mitochondria play various roles that are important for cell function and survival; therefore, significant mitochondrial dysfunction may have chronic consequences that extend beyond the cell. Mitochondria are already susceptible to damage, which may be exacerbated by environmental exposures. Therefore, the aim of this review is to summarize the recent literature (2012-2022) looking at the effects of six ubiquitous classes of compounds on mitochondrial dysfunction in human populations.

Recent findings: The literature suggests that there are a number of biomarkers that are commonly used to identify mitochondrial dysfunction, each with certain advantages and limitations. Classes of environmental toxicants such as polycyclic aromatic hydrocarbons, air pollutants, heavy metals, endocrine-disrupting compounds, pesticides, and nanomaterials can damage the mitochondria in varied ways, with changes in mtDNA copy number and measures of oxidative damage the most commonly measured in human populations. Other significant biomarkers include changes in mitochondrial membrane potential, calcium levels, and ATP levels. This review identifies the biomarkers that are commonly used to characterize mitochondrial dysfunction but suggests that emerging mitochondrial biomarkers, such as cell-free mitochondria and blood cardiolipin levels, may provide greater insight into the impacts of exposures on mitochondrial function. This review identifies that the mtDNA copy number and measures of oxidative damage are commonly used to characterize mitochondrial dysfunction, but suggests using novel approaches in addition to well-characterized ones to create standardized protocols. We identified a dearth of studies on mitochondrial dysfunction in human populations exposed to metals, endocrine-disrupting chemicals, pesticides, and nanoparticles as a gap in knowledge that needs attention.

Keywords: Environmental chemicals; Heteroplasmy; Mitochondrial dysfunction; Oxidative stress; mtDNA.

Fig. 1

Common biomarkers used to identify and measure mitochondrial dysfunction. mtDNA mitochondrial DNA, Ca²⁺ calcium ions, 8-OHdG 8-oxo-2′-deoxyguanosine

Fig. 2

The environmental toxicant–induced mitochondrial dysfunction pathways discussed within this review. Blue boxes outlining the environmental toxicants represent associations shown in both human populations and experimental models, whereas red boxes represent associations found only in experimental models