April 26, 2013
Researchers Discover Key Protein In Development Of Parkinson’s Disease
Brett Smith for redOrbit.com - Your Universe Online
By working with mouse and fruit fly hearts, researchers at Washington University (WUSTL) School of Medicine, St. Louis identified a key protein that has a connection with 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,” senior author Dr. Gerald W. Dorn II, MD, a professor of Medicine at WUSTL, said in a statement. “This suggested they are somehow related, and now we have identified a fundamental mechanism that links the two.”
Mitochondria are known as the power plant of the cell and heart cells rely on large numbers on mitochondria to keep functioning. If cells allow poorly functioning mitochondria to build up, the results can be catastrophic. Healthy cells typically identify bad mitochondria and remove them.
Researchers have been working since 2006 to identify the mysterious middle section of the chain that causes the disruption of sick mitochondria's ability to communicate to the rest of the cell it needs to be destroyed.
“This was a big question,” Dorn said. “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,” he added. “And until recently, I don´t think anybody would have looked. This isn´t what Mfn2 is supposed to do.”
Normally, mitochondria import and then destroy a molecule called PINK. When mitochondria aren´t functioning properly, they can´t destroy PINK and its levels begin to rise.
The WUSTL researchers found once PINK concentration reaches a certain level, the molecule makes a chemical change to Mfn2, which is located on the surface of mitochondria. The altered Mfn2 then binds the mitochondria to a molecule called Parkin within the surrounding cell. After binding to Mfn2, Parkin labels the sick mitochondria for destruction by the cell.
“But if you have a mutation in PINK, you get Parkinson´s disease,” Dorn said. “About 10 percent of Parkinson´s disease is attributed to these or other mutations that have been identified.”
According to the researchers, their discovery could help improve the diagnosis for both Parkinson´s disease and heart failure.
“I think researchers will look closely at inherited Parkinson´s cases that are not explained by known mutations,” Dorn explained. “They will look for loss of function mutations in Mfn2, and I think they are likely to find some.”
The cardiologist said his medical team has already detected mutations in Mfn2 that could explain certain familial forms of heart failure.
“In this case, the heart has informed us about Parkinson´s disease, but we may have also described a Parkinson´s disease analogy in the heart,” he said. “This entire process of mitochondrial quality control is a relatively small field for heart specialists, but interest is growing.”