Scientists have discovered how cells initiate waste recycling and form ‘garbage bags,’ a crucial process for health. This breakthrough may pave the way for future drugs to combat Parkinson’s, Alzheimer’s, and support healthy aging.
An international research team has uncovered how cells initiate their recycling process by forming “garbage bags” to remove unwanted proteins.
Co-led by the Walter and Eliza Hall Institute (WEHI) and published in Science, the study provides new insights into cellular waste disposal, which could contribute to future treatments for neurodegenerative diseases like Parkinson’s and Alzheimer’s.
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 aging and target diseases like Parkinson’s and beyond. Credit: WEHI
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 unraveled 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 aging and target diseases like Parkinson’s and beyond.”
Reference: “Structural pathway for PI3-kinase regulation by VPS15 in autophagy” by Annan S. I. Cook, Minghao Chen, Thanh N. Nguyen, Ainara Claveras Cabezudo, Grace Khuu, Shanlin Rao, Samantha N. Garcia, Mingxuan Yang, Anthony T. Iavarone, Xuefeng Ren, Michael Lazarou, Gerhard Hummer and James H. Hurley, 6 February 2025, Science.
DOI: 10.1126/science.adl3787
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.
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