Mitochondria: discovering environmental sensors and mediators
Each human and animal cell contains between several hundred and >1,000 mitochondria, each carrying 2–10 copies of mitochondrial DNA. Mitochondria are not only a primary target of environmental oxidative damage, but – more importantly – damaged mitochondria promptly accelerate intra-cellular oxidation. A large variety of environmental exposures and risk factors produce oxidative stress. Due to the paucity of repair mechanisms and diminished protective histones, mitochondrial DNA is expected to accumulate oxidative damage and thus provide a molecular archive of past environments and aggregate risk. Consistent with this hypothesis, we recently showed that air pollution and lead increase the blood abundance of mitochondrial DNA molecules, a marker of damaged, dysfunctional mitochondrial DNA, by up to 50%.
Following these groundbreaking results, we have established a program of environmental mitochondriomics in the lab. We propose that mitochondria are uniquely sensitive to environmental toxicants. We are using sensitive techniques to identify the degree of environmental oxidation of the mitochondrial DNA. We have been investigating the effects of environmental factors not only on mitochondrial DNA abundance, but also on mutations and deletions of the mitochondrial genome. Because of the central roles of oxidation and mitochondria in environmental causation of disease, mitochondriomics could provide models that can be applied to a variety of risk factors and health-related conditions.