Bennett Van Houten, Ph.D.
University of Pittsburgh
NIEHS grantees demonstrated for the first time that damaged mitochondria, the powerhouses of a cell, can trigger a harmful chain reaction that results in telomere damage. Telomeres protect the ends of chromosomes and play an important role in cell division and aging.
The team developed and used a new targeted approach to study mitochondrial damage that generates a short-lived, highly reactive singlet oxygen, a type of harmful reactive oxygen species (ROS) inside the mitochondria when exposed to light. ROS are chemically reactive molecules involved in inflammation, aging, and cancer. The researchers observed that exposure to this singlet oxygen resulted in decreased mitochondrial function and mitochondrial fragmentation, an important early event that can lead to cell death. They also found that the singlet oxygen produced a persistent secondary wave of ROS within the mitochondria.
By following the movement of ROS, they reported direct evidence that mitochondrial ROS can travel to the cell nucleus and damage telomeres, causing fragility and DNA double strand breaks in this important region. In a similar experiment in cells without mitochondrial DNA, they reported no ROS accumulation and no telomere damage.
According to the authors, their findings may represent a key event that produces favorable conditions for cancer cells by creating a feedback loop that amplifies cell damage, particularly DNA damage at telomeres. They suggest this chain of events may underlie the molecular processes involved in cancer and other diseases.
Citation: Qian W, Kumar N, Roginskaya V, Fouquerel E, Opresko PL, Shiva S, Watkins SC, Kolodieznyi D, Bruchez MP, Houten BV. 2019. Chemoptogenetic damage to mitochondria causes rapid telomere dysfunction. Proc Natl Acad Sci U S A 116(37):18435−18444.