Scicence: hypoxic environment relieves lethal mitochondrial disease
Release date: 2016-03-01
- - For most creatures on Earth, oxygen means life. But biology is often very complex, and a recent article by the team of mitochondrial biologist Vamsi Mootha from Massachusetts General Hospital in Science magazine suggests the opposite. Mitochondria are "energy supply stations" in cells that can cause some serious mitochondrial diseases if they fail. For some patients with mitochondrial disease, high concentrations of oxygen can be fatal. For cells with mitochondrial dysfunction, a hypoxic environment may be more suitable for their survival and maintenance of "normal" work. The current experimental results are only from in vitro cell experiments, zebrafish and mouse model experiments. From the experimental results, hypoxia therapy may provide some help for some rare but fatal diseases.
First, researchers use a common CRISPR DNA editing technique to knock out 18,000 genes that have changed in mitochondrial diseases in cells. I hope that when a specific gene is knocked out, cells that are defective in mitochondrial function can survive. After a massive screening, they finally confirmed the VHL gene, which is a suppressor of cellular hypoxia. The VHL genes were knocked out in animal models, and they showed hypoxic symptoms even under normal conditions.
Next, they found in the zebrafish mitochondrial dysfunction model that if VHL was inactivated, their survival would be doubled. They then completed another experiment in a mouse model of human mitochondrial disease (subacute necrotic encephalomyelopathy). They allowed mice to survive for 2 months under hypoxic conditions, and the survival of mice under hypoxic conditions was extended by more than 6 months compared with normal-treated mice.
Mootha's team is still trying to explain why hypoxia improves survival in mice with mitochondrial disease. "This is contrary to common sense, but it gives us a new understanding of mitochondrial disease research." Although hypoxia inhibits the production of ATP, it also weakens the production of free radicals that attack cells and harm tissues. This free radical is also responsible for some children's mitochondrial diseases. On the other hand, the team tried to help the cells and the body function properly by activating other alternative mitochondrial ATP production pathways with hypoxia.
For patients, continuous hypoxic therapy is not shown, and hypoxic cells can accelerate cancer. Therefore, other methods can be considered to control hypoxia. For example, treatment of mitochondrial dysfunction by some drug induction will be a good research direction.
Source: Bio Valley
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