Scientists have finally pinned down a protein that’s largely responsible for Parkinson’s disease. Known as PINK1, the protein has been linked to the disease for decades but its structure and how to switch it back on have remained elusive – until now.
When it’s functioning properly, PINK1 plays a vital role in cellular recycling processes. The protein detects when energy-producing structures called mitochondria become damaged, and will gather on their surface. PINK1 then signals for other proteins to help remove the broken component, to allow new ones to grow in its place.
Unfortunately, mutations in PINK1 can interrupt this process, causing damaged mitochondria to build up on cells – eventually killing them. The effect is particularly pronounced for cells that are very energy-hungry, like brain cells – causing the gradual degeneration seen with Parkinson’s disease.
PINK1’s role in Parkinson’s has been known for a long time, but frustratingly the protein’s structure, and how it attaches to mitochondria, have remained a mystery. That makes it hard to treat the disease. Now, researchers at WEHI in Australia have managed to image the structure of PINK1 attached to mitochondria for the first time, using cryo-electron microscopes.
“This is the first time we’ve seen human PINK1 docked to the surface of damaged mitochondria and it has uncovered a remarkable array of proteins that act as the docking site,” said Dr. Sylvie Callegari, lead author of the study. “We also saw, for the first time, how mutations present in people with Parkinson’s disease affect human PINK1.”
The proteins that make up the so-called docking site are important pieces of the puzzle that were, until now, missing. They provide a whole host of potential targets that could help reactivate the PINK1 protein so that it can perform its job properly once again.
“Our structure reveals many new ways to change PINK1, essentially switching it on, which will be life-changing for people with Parkinson’s,” said Professor David Komander, corresponding author of the study. “This is a significant milestone for research into Parkinson's. It is incredible to finally see PINK1 and understand how it binds to mitochondria.”
The next steps are to try to use this new information to find drugs that can switch PINK1 back on, which could help slow or stop progression of Parkinson’s disease.
The research was published in the journal Science.
Source: WEHI via Eurekalert
