Mitochondria as a target of environmental toxicants

Abstract

Enormous strides have recently been made in our understanding of the biology and pathobiology of mitochondria. Many diseases have been identified as caused by mitochondrial dysfunction, and many pharmaceuticals have been identified as previously unrecognized mitochondrial toxicants. A much smaller but growing literature indicates that mitochondria are also targeted by environmental pollutants. We briefly review the importance of mitochondrial function and maintenance for health based on the genetics of mitochondrial diseases and the toxicities resulting from pharmaceutical exposure. We then discuss how the principles of mitochondrial vulnerability illustrated by those fields might apply to environmental contaminants, with particular attention to factors that may modulate vulnerability including genetic differences, epigenetic interactions, tissue characteristics, and developmental stage. Finally, we review the literature related to environmental mitochondrial toxicants, with a particular focus on those toxicants that target mitochondrial DNA. We conclude that the fields of environmental toxicology and environmental health should focus more strongly on mitochondria.

Keywords: contaminants; mitochondria; mitochondrial DNA; mitochondrial disease.; mitochondrial toxicity.

Fig. 1.

Mitochondrial morphology. Panel (A) shows the mitochondrial network (MitoTracker Red-stained) containing many mtDNA nucleoids (PicoGreen-stained) surrounding the nucleus (Hoescht-stained) of a human primary fibroblast (photo: Amanda Bess). Panels (B) and (C) show a transgenic strain of C. elegans that expresses a mitochondrial matrix-targeted green fluorescent protein in body wall muscle cells. The image in panel (B) is from a control nematode, and the image in panel (C) is from a nematode exposed to 1µM carbonyl cyanide m-chlorophenyl hydrazone, a potent ionophore and inhibitor of oxidative phosphorylation that leads to mitochondrial fragmentation; the mitochondrial matrix was visualized via expression of green fluorescent protein (photo: John Rooney).

Fig. 2.

Factors that affect mitochondrial vulnerability to environmental toxicants, as discussed in the text.