Low Oxygen Slows Mitochondrial Disease, Fellow Finds

Monday, February 29, 2016

Less oxygen is generally bad for animals, but fellow Isha Jain and colleagues at Harvard University, Massachusetts General Hospital and the Massachusetts Institute of Technology found a situation in which the opposite may be true.

In a paper in the prestigious journal Science, they report that low-oxygen environments countered the effects of mitochondrial disease in mice. The discovery could help identify causes and treatments for this rare condition in humans.

Mitochondria are the cell’s power plants, producing energy-storing molecules and moving them through cells. Flaws in mitochondrial DNA or cellular DNA that control these organelles can lead to muscle weakness, slow growth and other problems, a Science feature article says.

Jain and her doctoral advisor, Vamsi Mootha, removed thousands of genes from human cells that were altered to have the same problems as in people with mitochondrial disease, the Science article states. They sought genes that, when removed, helped cells survive mitochondrial malfunctions.

One gene had a strong effect. Deactivating it made cells behave as if they were in a low-oxygen environment. The researchers then took mice engineered to have a version of human mitochondrial disease and kept them in containers designed to replicate the thin air found at high altitudes. They lived for more than six months, compared to just two months for mice kept in a standard oxygen environment.

The researchers are trying to understand why low oxygen levels helped the mice survive. What they learn could lead to new treatments, including low-oxygen therapies or drugs to alter the genetic pathway controlling the cell’s response.

Jain is a third-year DOE CSGF recipient in computer science and systems biology at MIT. She earned her bachelor’s degree in chemical and physical biology from Harvard in 2012. She talks about her research and the fellowship in this video.