Environmental pollution is a major global health problem, responsible for around nine million premature deaths a year, according to a recent publication in The Lancet Planetary Health. The study found that ambient air pollution and toxic chemicals created by increasing 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.referring to the publication during his NIEHS Keystone Scientific Conference on July 20. “Keeping up with new chemicals in the environment and understanding which ones really matter from a human health perspective is crucial.”
His lab focuses on how pollutants affect mitochondria — tiny organelles in our cells that produce energy — and potentially influence disease. Toxicology tests have indicated that many environmental agents target mitochondria, and Meyer aims to shed light on how such exposures can pave the way to poor health.
Advancing key scientific knowledge
“Mitochondria are obviously involved in energy generation and the regulation of cellular apoptosis,” Meyer said. (Apoptosis refers to programmed cell death. Learn more about its important biological functions.) “But they also do a lot of other things. They’re involved in calcium homeostasis, thermogenesis, steroid and heme synthesis, innate immunity, and epigenetics.
With this diversity of biological roles comes a diversity of harm when things go wrong, Meyer noted. Diabetes, cancer, metabolic syndrome and neurodegenerative diseases have all been linked to mitochondrial dysfunction, he told participants.
Daniel Shaughnessy, Ph.D., NIEHS Scientific Health Administrator, and Leroy Worth, Ph.D., Scientific Review Officer at the institute, co-hosted Meyer’s talk.
“Given the central role of mitochondria in a variety of important cellular processes, assessing how toxic exposures affect mitochondrial function is critical as it will help us better understand how cells respond to environmental stress,” Shaughnessy said. . “Dr. Meyer’s research on mitochondrial toxins has important implications for our understanding of the risks of multiple diseases across the lifespan.
Developmental origins of the disease
In 2021, Meyer’s lab showed that in Caenorhabditis elegans, which is a model nematode worm often used in environmental toxicology studies, early 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 toxic substances. 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 carcinogenic.
Despite the fact that mitochondrial DNA damage was removed by natural processes, over time worms exposed to UVC showed much lower energy levels than worms that were not, observed Meyer and his team.
“One of the big effects we saw was that ATP levels, which normally rise when a worm reaches adulthood and then fall back in older life, followed the same pattern in UVC-exposed worms. , but were consistently, throughout life, 30-50% lower,” he said.
The study suggests that exposure to toxic chemicals can affect organisms differently depending on their exposure history, according to Meyer.
“I would also note that individuals with differences in mitochondrial protein-coding genes, such as disease genes and possibly allelic variants, are likely to be at greater risk for toxic effects from these exposures,” a- he added. “Alternatively, exposures could trigger the presentation of a genetically caused 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 Laboratory website.
Quote: 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. Mitochondrial DNA damage in early life results in lifelong deficits in redox signaling-mediated energy production in Caenorhabditis elegans. ORP Biol 43:102000.
(Lindsay Key is a contract writer for the NIEHS Office of Communications and Public Liaison.)