Environmental pollution is a major global health problem, responsible for approximately nine million premature deaths per year, according to a recent publication in The Lancet Planetary Health. The study found that ambient air pollution and toxic chemicals created by increased industrialization and urbanization pose the greatest threat to human health.
“I think it’s worth asking — what do we know about these chemicals?” said Duke University Associate Professor Joel Meyer, Ph.D.referencing the publication during his NIEHS Keystone Science Lecture on July 20. “Keeping up with new chemicals in the environment and understanding which ones really matter from a human health standpoint is crucial.”
His lab focuses on how pollutants affect mitochondria — tiny organelles in our cells that produce energy — and potentially influence disease. Toxicological tests have indicated that many environmental agents target mitochondria, and Meyer aims to shed light on how such exposures can pave the way for ill health.
Advancing key scientific knowledge
“Mitochondria are obviously involved in energy generation and regulating cell apoptosis,” said Meyer. (Apoptosis refers to programmed cell death. Learn more about its important biological functions.) “But they do lots of other things, too. They’re involved in calcium homeostasis, thermogenesis, steroid and heme synthesis, innate immunity, and epigenetics.”
With that diversity of biological roles comes a diversity of ailments when things go wrong, noted Meyer. Diabetes, cancer, metabolic syndrome, and neurodegenerative conditions have all been linked to mitochondrial dysfunction, he told attendees.
NIEHS Health Scientist Administrator Daniel Shaughnessy, Ph.D., and Leroy Worth, Ph.D., a Scientific Review Officer at the institute, co-hosted Meyer’s talk.
“Given the central role for mitochondria in a variety of important cellular processes, it is critical to assess how toxicant exposures affect mitochondrial function because that will help us better understand how cells respond to environmental stress,” said Shaughnessy. “Dr. Meyer’s research on mitochondrial toxicants has important implications in our understanding of the risks for multiple diseases across the lifespan.”
Developmental origins of disease
In 2021, Meyer’s lab showed that in Caenorhabditis elegans, which is a nematode worm model often used in environmental toxicology studies, early-life exposure to low levels of ultraviolet C (UVC) resulted in mitochondrial DNA damage. Such damage caused health problems later in life, including increased sensitivity to other toxicants. Humans are not normally exposed to UVC, which is blocked by the ozone layer, but its effects are similar to those caused by polycyclic aromatic hydrocarbons and aflatoxin B1, which is a carcinogen.
Despite the fact that the mitochondrial DNA damage was removed by natural processes, over time, worms exposed to UVC showed much lower energy levels than worms that were not, Meyer and his team observed.
“One of the big effects we saw was that ATP levels, which normally go up as a worm reaches adulthood and then back down in older life, followed the same pattern in the UVC-exposed worms but were routinely, throughout life, 30 to 50 % lower,” he said.
The study suggests that exposure to toxic chemicals can affect organisms differently depending on their exposure history, according to Meyer.
“I’d also note that individuals with differences in genes encoding mitochondrial proteins, such as disease genes and possibly allelic variants, are likely to be at greater risk of toxic effects of those exposures,” he added. “Alternately, exposures might trigger the presentation of genetically-based mitochondrial disease. This is critical because at least 1 in 5,000 people suffer from mitochondrial disease.”
To learn more about research in this area, visit the Meyer Lab’s website.
Citation: Hershberger KA, Rooney JP, Turner EA, Donoghue LJ, Bodhicharla R, Maurer LL, Ryde IT, Kim JJ, Joglekar R, Hibshman JD, Smith LL, Bhatt DP, Ilkayeva OR, Hirschey MD, Meyer JN. 2021. Early-life mitochondrial DNA damage results in lifelong deficits in energy production mediated by redox signaling in Caenorhabditis elegans. Redox Biol 43:102000.
(Lindsay Key is a contract writer for the NIEHS Office of Communications and Public Liaison.)