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Lower Oxygen Intake Improves Symptoms and Survival in Mice with Mitochondrial Disease

Elite athletes know how to get the most bang out of their mitochondria, often training at high elevations to force their bodies to work more efficiently in “thinner air.” Endurance increases, recovery time decreases, and mitochondrial capacities change, allowing the athletes to work harder and perform better.

Mitochondria are the power centers of the cell, producing 90 percent of the body’s energy requirements. Mitochondrial disease directly impacts the cells’ mitochondria, impairing the mitochondria’s ability to make the energy necessary to fuel the cells and, ultimately, body organs. Mitochondrial diseases are inherited chronic illnesses that cause debilitating physical, developmental, and cognitive disabilities with symptoms including poor growth, loss of muscle coordination, muscle weakness and pain, seizures, vision and/or hearing loss, gastrointestinal issues, learning disabilities, and organ failure. It is estimated that 1 in 4,000 people has “Mito” (http://www.mitoaction.org/mito-faq).

Vamsi Mootha, along with his team of Harvard Medical School and Mass General Hospital investigators, recently published promising laboratory results in the journal Science regarding lower oxygen exposure in mice with mitochondrial disease. In fact, mice with Leigh’s disease, the most common pediatric mitochondrial disease, fared better in chronically low oxygen levels, similar to levels found at higher elevations. The study mice had dramatic reduction of typical disease symptoms and significantly extended survival rates. Many may initially think that exposure to lower oxygen levels would harm struggling mitochondria further, but Mootha’s research indicates the opposite to be true. Mootha and his team speculate that exposure to lower levels of oxygen in the air may signal inborn adaptive responses that activate non-mitochondrial-dependent energy production. 

“The thinner air is less toxic to the mice with mitochondrial disease,” states Mootha, HMS professor of systems biology and a researcher in the Mass General Department of Molecular Biology. Humans have elaborate responses to cope with energy metabolism at high altitudes and low oxygen levels, yet the cellular mechanism of these responses is not fully understood. Mootha's team continues to work on determining exactly why the mice fare better on the cellular level.

Mootha emphasizes that researchers are still a few years away from studies or therapeutic options for humans as all work to date has been limited to cell lines and mice. Common knowledge clearly shows that oxygen levels that are too low are very harmful to humans. Breathing air with low oxygen levels reduces oxygen delivery to organs and produces toxicities. Animal studies are crucial to determine optimal treatment regimens and long-term safety. Establishing therapeutic levels of lowered oxygen in mice with Leigh’s disease, and then mice with other mitochondrial diseases, is vital to eventually knowing if and when to apply this therapy to humans in a safe and effective manner.

Fueling hope for future treatment for mitochondrial disease, Mootha concludes:

“Independent of our current work … I think we're witnessing a sea change in the area of mitochondrial therapeutics. This is such an exciting time. A few years ago there were no clinical trials for mitochondrial disease -- and now, there are at least three new experimental drugs in trials. There is growing appreciation for the fundamental role for mitochondria in common disease, which is fueling broad research on mitochondria. I'm quite optimistic that in the coming years we will start seeing fundamentally new and effective drugs for mitochondrial disease.”

Additional Reading:

Hypoxia as a therapy for mitochondrial disease: http://science.sciencemag.org/content/early/2016/02/24/science.aad9642

The body's response to low levels of oxygen may treat mitochondrial disease, study finds: http://www.massgeneral.org/about/pressrelease.aspx?id=1903

Into Thin Air: https://hms.harvard.edu/news/thin-air

Oxygen deprivation counters deadly mitochondrial disease in animals:  http://www.sciencemag.org/news/2016/02/oxygen-deprivation-counters-deadly-mitochondrial-disease-animals

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