Researchers have discovered a missing link in understanding how damage to mitochondria - the body's 'power house' - leads to Parkinson's disease and even some forms of heart failure.
Mitochondria manufacture the energy the cell requires to perform its many duties.
Working in mouse and fruit fly hearts, the researchers at Washington University School of Medicine in St Louis 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 were published 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 per cent higher risk of dying from heart failure," said senior author Gerald W Dorn II, 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," said Dorn.
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, researchers said.
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.
Specifically, mitochondria work to import a molecule called PINK. Then they work to destroy it. When mitochondria get sick, they can't destroy PINK and its levels begin to rise.
Once PINK levels get high enough, they make a chemical change to Mfn2, which sits on the surface of mitochondria.
Once Parkin binds to Mfn2 on sick mitochondria, Parkin labels the mitochondria for destruction. The labels then attract special compartments in the cell that "eat" and destroy the sick mitochondria.
According to Dorn, the discovery of Mfn2's relationship to PINK and Parkin opens the doors to a new genetic form of Parkinson's disease. And it may help improve diagnosis for both Parkinson's disease and heart failure.
