Proper function of cell ‘powerhouse’ is essential to survival, says chief of UW Medicine mitochondria research center.
Charlie Gard, the British baby at the center of an international debate over whether to sustain life–support, has a genetic disorder called infantile onset encephalomyopathic mitochondrial DNA depletion syndrome, or MDDS.

Gard, 11 months, inherited defective genes from his parents for a protein crucial to normal mitochondrial function. MDDS appears shortly after birth and progresses relentlessly. Since birth, Charlie has grown increasingly weak, such that his doctors say he cannot now move or breathe on his own. His condition has no known effective treatment.

"Mitochondria are known as the cell’s powerhouses because they generate almost all the energy that our cells need to live," said Dr. Rong Tian. "Without functioning mitochondria, cells begin to die within minutes.” Tian directs the UW Medicine Mitochondria and Metabolism Center and is a professor of anesthesiology and pain medicine at the University of Washington School of Medicine. Physicians at London’s Great Ormond Street Hospital who have cared for the boy determined that the damage to his brain had progressed so far that the most humane course would be to withdraw Charlie’s life support. Britain’s High Court and the European Human Rights Commission supported that recommendation.

Charlie’s parents argued that he should be allowed to receive an unproven treatment offered by a New York neurologist. The treatment is for a different form of the disease. Britain’s High Court has agreed to reconsider the case to determine whether the proposed therapy is likely to help the child.

Mitochondria appear to be descendants of bacteria that entered into cells and took up residency early in our evolution. Over time, they have become highly specialized, losing their ability to live independently. Yet they still have their own genes that are arranged in a circular chromosome and are distinct from the genes found in our chromosomes.

“Pure mitochondrial diseases, such as that affecting the child in Britain, are rare,” Tian said, and result from mutations in the genes in the mitochondria’s circular chromosome or mutations in the cellular genes. Evidence is mounting that mitochondrial function is impaired by heart disease, neurodegenerative diseases such as Parkinson’s, and diabetes, as well as by the process of normal aging, Tian said.

Her research focuses on how mitochondria respond to stresses brought on by disease. She and her colleagues have found that, in addition to generating energy, mitochondria also regulate calcium levels in the cell and generate molecules that can quickly alter the function of proteins throughout the cell. These regulatory activities help cells adapt to new demands and stresses.

In many cases, mitochondria ultimately control a cell’s fate, Tian said; severe stress can trigger a mitochondrial reaction that causes the cell to die – resulting, for instance, in tissue injury from heart attacks or kidney disease.

“If we can develop drugs that can help protect mitochondria from these stresses, we might be able to mitigate or even halt the progression of these diseases,” Tian said.