Discovery of key proteins that regulate mitophagy could unlock new Parkinson's disease treatments Researchers At WEHI ...

Walter and Eliza Hall InstituteJul 23 2024

Researchers at WEHI in collaboration with a team at the University of Vienna have discovered two proteins that act as regulators for mitophagy.

Mitophagy is the process cells use to recycle damaged mitochondria, the source of cell energy, and dysfunction of this process has been linked to Parkinson's disease. 

The discovery, a co-led by Associate Professor Michael Lazarou at WEHI and Professor Sascha Martens at the University of Vienna, opens a new avenue for researchers to boost mitophagy activity, to promote mitochondrial and neuronal health. 

At a glance 

•  Mitophagy dysfunction, especially PINK1/Parkin dependent mitophagy, has been linked to Parkinson's disease. 

• Researchers have discovered two proteins, NAP1 and SINTBAD, that are involved in the regulation of mitophagy activation in cells. 

• The discovery opens a new avenue for researchers to boost mitophagy activity, which in turn can promote mitochondrial and neuronal health. 

Parkinson's disease is the world's fastest growing neurological condition. Currently there are no drugs or therapies that slow or stop the progression of the disease. 

In Australia, someone is diagnosed with Parkinson's approximately every 30 minutes. Current estimates show there are over 219,000 people living with Parkinson's in Australia, a number forecast to double in the next 15 years. 

WEHI's Parkinson's Disease Research Centre has some of the world's leading researchers tackling the problem using a multi-disciplinary collaborative approach. 

New proteins linked to Parkinson's pathway 

Mitochondria are the energy generating machines in our cells and are kept healthy by mitophagy, which is the molecular process of removing or recycling damaged or dysfunctional mitochondria. 

PINK1 and Parkin are two key genes involved in mitophagy, and mutations in these genes are linked to early-onset Parkinson's disease. 

Until the discovery of two proteins, NAP1 and SINTBAD, exactly how PINK1/Parkin mitophagy activation was regulated was unknown. 

The new research, published in Nature Structural and Molecular Biology, has revealed that NAP1/SINTBAD function by regulating the threshold for mitophagy activation. 

Associate Professor Michael Lazarou said the discovery of NAP1/SINTBAD expands our understanding of how mitophagy is regulated and adds a fresh area of focus for researchers to target in their search for drug therapies. 

"Targeting these proteins in neurons could be a potential avenue to boost mitophagy by lowering the activation threshold, which in turn can promote mitochondrial and neuronal health." 

What does this mean for people with Parkinson's?  

For people living with Parkinson's disease there are no drugs to slow or stop the progression of the disease, which affects movement as well as non-motor symptoms such as mood, sleep, memory and speech difficulties. 

It is hoped this research, in combination with expertise from WEHI's National Drug Discovery Centre, will drive further research into finding targets for drug development and deliver opportunities for developing new therapies aimed at targeting neurodegenerative conditions such as Parkinson's. 

The research was supported by Aligning Science Across Parkinson's (ASAP) and the Rebecca Cooper Medical Research Foundation.