Cellular clean-up: Solving the mystery of how cells recycle

A new discovery from an international collaborative research team has solved the mystery of how cells turn on their recycling process and create ‘garbage bags’ to remove proteins.

The study, co-led by WEHI and published in Science, sheds new light on how cells get rid of waste and could help towards finding future cures for neurodegenerative diseases such as Parkinson’s and Alzheimer’s.

Watch and embed the video: https://youtu.be/1vg9ej4kgwE

At a glance

• The process of how cells recycle waste is crucial to maintaining health, but how it is controlled and turned on has not been understood.

• An international collaboration co-led by WEHI, Max Planck Institute and University of California, Berkeley has now discovered how cells turn on recycling and make cellular ‘garbage bags’.

• It’s hoped this discovery, published in Science, will lead in future to drugs that will help the fight against diseases like Parkinson’s and Alzheimer’s, while also promoting healthy ageing.

Importance of cellular recycling

The process of how cells get rid of waste and recycle useful materials, called autophagy, is critical to health. 

In some conditions such as Parkinson’s and Alzheimer’s disease, cell waste accumulates, causing protein build-ups due to the recycling signals not working properly.

The new study, co-led by WEHI’s Professor Michael Lazarou, Professor Gerhard Hummer from the Max Planck Institute and Professor James H. Hurley from University of California, Berkeley, has unravelled one of the key cellular processes that govern autophagy.

The research team found how this process is controlled by a complex group of proteins, that add a molecular signal to a cell membrane. 

This signal is a critical step in switching on the autophagy process, allowing for the formation of cellular ‘garbage bags’ so that the damaged materials within cells can be recycled.

“We know that cellular recycling is absolutely fundamental to our overall health but we've struggled to understand precisely how this complex process is regulated – and how we can fix it when it breaks," said Prof Lazarou from WEHI’s Parkinson’s Disease Research Centre and Monash University’s Biomedicine Discovery Institute.

“In our team’s new study, we discovered surprising ways those cellular ‘garbage bags’ are created and how this group of proteins is regulated. Crucially, we found the switch that kickstarts the process. 

“Now we know how this recycling process is switched on we hope that knowledge will in future lead to new treatments that can turn on that process to promote healthy ageing and target diseases like Parkinson’s and beyond.”

An international collaboration

The research is part of an international research grant through the Aligning Science Across Parkinson’s collaborative network, which fosters collaboration to better understand the underlying causes of Parkinson’s disease. Their aims of scale, transparency and open access data sharing are designed to accelerate the pace of discovery and find a cure for Parkinson’s.

The WEHI Parkinson’s Disease Research Centre is also a member of ASAP’s Global Parkinson’s Genetic Program, a collaboration working to unlock the genetic architecture of Parkinson’s disease.

The study, “Structural pathway for PI 3-kinase regulation by VPS15 in autophagy”, with co-first authors Thanh Nguyen (WEHI, Monash University, Annan Cook (University of California, Berkeley), Minghao Chen (University of California, Berkeley) and Ainara Claveras Cabezudo (Max Planck Institute), is published in Science (DOI: 10.1126/science.adl3787).

Images and captions

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Professor Michael Lazarou, co-corresponding author.

Autophagy_Science_1_WEHI
The cell recycling process, known as autophagy, is controlled by a complex group of proteins. This 3D image reveals the overall structure of the autophagy promoting complex, showing each of its individual components in different colours.

Video
https://youtu.be/1vg9ej4kgwE  
This video shows how a rotational mechanism in the autophagy promoting complex switches it on, so that it can drive the formation of cellular ‘garbage bags’. By identifying the switch that kickstarts the cell recycling process, researchers hope to work towards new treatments that can turn on autophagy to promote healthy ageing and target diseases like Parkinson’s and beyond.