The researchers at Melbourne’s Walter and Eliza Hall Institute (WEHI) have unveiled a critical discovery that explains a longstanding enigma related to a protein’s function in removing damaged mitochondria from the body. This could lead to the creation of innovative therapies for Parkinson’s disease.
The study provides answers to the age-old questions about Optineurin, a protein that is predominantly present in the human brain. This protein assists the body in eliminating malfunctioning mitochondria, which are minuscule structures essential for proper body function. If these mitochondria deteriorate, they can lead to various illnesses, including Parkinson’s, a condition with no known cure.
Mitochondria are essential for generating energy in cells, and their damage can profoundly affect cellular function and cause different diseases. Damaged mitochondria are generally eliminated through a process called ‘mitophagy.’
Two essential proteins, PINK1 and Parkin, tag the faulty mitochondria for destruction. In Parkinson’s disease, mutations in these proteins may lead to a buildup of damaged mitochondria in the brain, causing symptoms like tremors and mobility issues.
The research, published in Molecular Cell, reveals how Optineurin recognizes the unhealthy mitochondria marked by PINK1 and Parkin, facilitating their removal through the body’s waste disposal mechanism.
Associate Professor Michael Lazarou, the study’s head, emphasizes that this finding fills a critical knowledge void and redefines our understanding of this cellular process. Optineurin’s unique way of connecting damaged materials to the body’s waste system sets it apart from similar proteins.
Understanding Optineurin’s role could enable targeted prevention of damaged mitochondria build-up in neurons, significantly impacting Parkinson’s disease, which affects over 10 million individuals globally.
A unique aspect of this discovery is that PINK1 acts as a monitoring system within the mitochondria, working with Parkin to form cellular ‘garbage bags’ around the damaged mitochondria, with Optineurin initiating this process.
The study disclosed that Optineurin binds to an enzyme called TBK1, activating a specific cellular mechanism to create these ‘garbage bags.’ Unlike other proteins, Optineurin relies on TBK1, marking a significant advancement in the pursuit of new treatments for Parkinson’s disease.
Dr. Thanh Nguyen, the first author, shared the ambitious goal of finding ways to increase PINK1/Parkin mitophagy in the body, particularly in the brain, to more efficiently remove damaged mitochondria. They also aim to design a molecule that could simulate what Optineurin does, potentially preventing damaged mitochondria’s accumulation without needing PINK1 or Parkin.
Dr. Nguyen acknowledged that the clinical implementation of these findings would take years but emphasized that this research had laid the groundwork needed to understand Optineurin’s functionality and identify it as a possible future therapeutic target.
In the next phase, the researchers plan to collaborate with WEHI’s Parkinson’s Disease Centre to further investigate Optineurin’s behavior and how it might be targeted to improve treatment options for individuals with mutations in PINK1/Parkin.
This groundbreaking research was conducted in collaboration with Professor Sascha Martens’ lab at the University of Vienna and received support from various health and research organizations, including the Michael J. Fox Foundation for Parkinson’s Research.
Table of Contents
Frequently Asked Questions (FAQs) about Optineurin
What is the significant discovery made by researchers at Melbourne’s Walter and Eliza Hall Institute (WEHI) concerning Parkinson’s disease?
The researchers have discovered the protein Optineurin’s role in clearing damaged mitochondria from the body. This understanding might lead to the development of new treatments for Parkinson’s disease.
How does the protein Optineurin function in the body?
Optineurin helps in removing damaged mitochondria by binding to an enzyme known as TBK1. It plays a unique and unconventional role in initiating the body’s garbage disposal process for malfunctioning mitochondria.
What is the potential impact of this discovery on Parkinson’s disease treatment?
Understanding Optineurin’s role and how it works with other proteins such as PINK1 and Parkin may lead to new ways of preventing the buildup of damaged mitochondria in neurons. This could be instrumental in developing new therapies for Parkinson’s disease, a condition affecting over 10 million people worldwide.
What are PINK1 and Parkin, and how are they related to Optineurin?
PINK1 and Parkin are proteins that are vital to the process of tagging malfunctioning mitochondria for destruction. The study reveals how Optineurin recognizes mitochondria ‘tagged’ by PINK1 and Parkin, enabling their delivery to the body’s garbage disposal system.
What is the next step in this research?
The next step is to work with WEHI’s Parkinson’s Disease Centre to validate the findings in neuronal model systems. This will provide further insight into how to target Optineurin and a related enzyme, TBK1, to enhance future treatment options for those with PINK1/Parkin mutations.
More about Optineurin
- Walter and Eliza Hall Institute (WEHI)
- Molecular Cell Journal
- Michael J. Fox Foundation for Parkinson’s Research
- National Health and Medical Research Council (NHMRC)
- Australian Research Council (ARC)
- Max Perutz Labs, University of Vienna
