Integrating mitochondriomics in children's environmental health

Abstract

The amount of scientific research linking environmental exposures and childhood health outcomes continues to grow; yet few studies have teased out the mechanisms involved in environmentally-induced diseases. Cells can respond to environmental stressors in many ways: inducing oxidative stress/inflammation, changes in energy production and epigenetic alterations. Mitochondria, tiny organelles that each retains their own DNA, are exquisitely sensitive to environmental insults and are thought to be central players in these pathways. While it is intuitive that mitochondria play an important role in disease processes, given that every cell of our body is dependent on energy metabolism, it is less clear how environmental exposures impact mitochondrial mechanisms that may lead to enhanced risk of disease. Many of the effects of the environment are initiated in utero and integrating mitochondriomics into children’s environmental health studies is a critical priority. This review will highlight (i) the importance of exploring environmental mitochondriomics in children’s environmental health, (ii) why environmental mitochondriomics is well suited to biomarker development in this context, and (iii) how molecular and epigenetic changes in mitochondria and mitochondrial DNA (mtDNA) may reflect exposures linked to childhood health outcomes.

Predictors of mitochondrial DNA copy number and damage in a mercury‐exposed rural Peruvian population near artisanal and small‐scale gold mining: An exploratory study

“…Mitochondrial function and integrity are critical to human health. A growing body of literature has identified multiple pathways through which mitochondria can be compromised, in particular, from pollutant exposures (Martinez and Greenamyre, ; Meyer et al, ; Brunst et al, ). Inference on the degradation of mitochondria following exposure to toxicants, such as organic chemicals, particulate matter, polycyclic aromatic hydrocarbons and cationic metals, has drawn largely upon controlled laboratory experiments using cell lines, model organisms or animal models (Bucio et al, ; Cakir et al, ; Karouna‐Renier et al, ; Sanders et al, ; Sanders et al, ).…”

“…In addition to MeHg, emerging epidemiological evidence suggests that mitochondria are affected by a variety of environmental factors, with many studies suggesting mtDNA biomarkers be used as estimates for pollutant exposure (DiMauro and Davidzon, 2005;Cakir et al, 2007;Hou et al, 2010;Martinez and Greenamyre, 2012;Hou et al, 2013;Meyer et al, 2013;Brunst et al, 2015;Zhong et al, 2016). Tobacco use has been associated with mitochondrial damage to bronchoalveloar lavage tissues (Ballinger et al, 1996) and buccal cells (Tan et al, 2008); air pollution with decreased mtDNA CN (Hou et al, 2010;Hou et al, 2013); and rotenone exposure with greater mtDNA damage in skeletal muscle (Sanders et al, 2014a).…”

Mitochondrial Toxicity

“…Will, Dykens, and colleagues beginning in 2007 ( Dykens et al , 2007 ; Dykens and Will, 2007 ; Marroquin et al , 2007 ) raised awareness of how common drug-induced mitochondrial toxicities were. Since then, the potential importance of mitochondrial toxicity as a mode of toxicity for many chemicals including drugs, pollutants, and others has been highlighted by several reviews ( Brunst et al , 2015 ; Meyer et al , 2013 ; Pereira et al , 2009 ; Sabri, 1998 ; Figure 1 ). Empirically, mitochondrial perturbations (most often, alterations in membrane potential) are one of the most common outcomes of in vitro toxicity screening efforts, including those of the National Toxicology Program ( Attene-Ramos et al , 2013 , 2015 ; Wills et al , 2015 ).…”

“…Efforts have been made to alert clinicians to the potential for mitochondrial toxicity, but these have been focused in large part on drugs ( Cohen, 2010 ). Pollutant-induced effects have begun to be examined both in wildlife ( Jayasundara, 2017 ) and human population studies ( Brunst et al , 2015 ; Zhong et al , 2017 ). However, there are several factors that complicate our ability to bridge laboratory and population studies.…”

A high-throughput screen for mitochondrial function reveals known and novel mitochondrial toxicants in a library of environmental agents

“…In recent times, the growing threat to the mitochondrial function by environmental pollutants/toxins has been highlighted by several reports (Brunst et al, 2015; Caito and Aschner, 2015; Meyer et al, 2013). Numerous environmental chemicals such as MPTP, rotenone, dimethylbenzanthracene (DMBA), and naphthalene are already known to negatively affect mitochondrial function, (Backer and Weinstein, 1980; Ernster et al, 1963; Harmon and Sanborn, 1982; Nicklas et al, 1987), and mitochondrial exposure to certain environmental compounds has been implicated in the etiology of some forms of Parkinson’s disease (Sherer et al, 2002).…”