Missing link in Parkinson's disease found: Discovery also has implications for heart failure

Apr. 25, 2013 Researchers at Washington University School of Medicine in St. Louis have described a missing link in understanding how damage to the body's cellular power plants leads to Parkinson's disease and, perhaps surprisingly, to some forms of heart failure.

These cellular power plants are called mitochondria. They manufacture the energy the cell requires to perform its many duties. And while heart and brain tissue may seem entirely different in form and function, one vital characteristic they share is a massive need for fuel.

Working in mouse and fruit fly hearts, the researchers found that a protein known as mitofusin 2 (Mfn2) is the long-sought missing link in the chain of events that control mitochondrial quality.

The findings are reported April 26 in the journal Science.

The new discovery in heart cells provides some explanation for the long known epidemiologic link between Parkinson's disease and heart failure.

"If you have Parkinson's disease, you have a more than two-fold increased risk of developing heart failure and a 50 percent higher risk of dying from heart failure," says senior author Gerald W. Dorn II, MD, the Philip and Sima K. Needleman Professor of Medicine. "This suggested they are somehow related, and now we have identified a fundamental mechanism that links the two."

Heart muscle cells and neurons in the brain have huge numbers of mitochondria that must be tightly monitored. If bad mitochondria are allowed to build up, not only do they stop making fuel, they begin consuming it and produce molecules that damage the cell. This damage eventually can lead to Parkinson's or heart failure, depending on the organ affected. Most of the time, quality-control systems in a healthy cell make sure damaged or dysfunctional mitochondria are identified and removed.

Over the past 15 years, scientists have described much of this quality-control system. Both the beginning and end of the chain of events are well understood. And since 2006, scientists have been working to identify the mysterious middle section of the chain -- the part that allows the internal environment of sick mitochondria to communicate to the rest of the cell that it needs to be destroyed.

"This was a big question," Dorn says. "Scientists would draw the middle part of the chain as a black box. How do these self-destruct signals inside the mitochondria communicate with proteins far away in the surrounding cell that orchestrate the actual destruction?"

"To my knowledge, no one has connected an Mfn2 mutation to Parkinson's disease," Dorn says. "And until recently, I don't think anybody would have looked. This isn't what Mfn2 is supposed to do."

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Missing link in Parkinson's disease found: Discovery also has implications for heart failure