A study conducted by a team from the Department of Fundamental Neuroscience at UNIL, published on June 5, 2023 in Neuron, reveals new insights into the autophagy mechanism in neurons and glial cells.
Autophagy is an essential process in cellular life: it allows for cleaning up waste produced by cellular machinery, eliminating unnecessary, defective, or toxic components, and recycling those that can be reused. This internal recycling factory then provides the cell with raw materials that are used to renew its constituents, such as proteins or organelles.
However, when this mechanism malfunctions, when autophagy dysfunctions, problems arise. Within brain cells, in neurons and glia, mutations in autophagy genes are linked to certain severe neurodevelopmental disorders, such as autism or epilepsy, or predispose to the development of neurodegenerative diseases later in life, such as Alzheimer’s or Parkinson’s.
How does autophagy work? First, waste materials are enclosed in a small sac-like structure called an autophagosome, which then fuses with the lysosome, another sac filled with enzymes. It is here that various residues – proteins, sugars, lipids, genetic material – are degraded into their basic constituents, building blocks that are subsequently reused by the cell. However, when autophagy is impaired, neurons and other brain cells accumulate damaged proteins and organelles that clutter their space and hinder their function.
While the importance of autophagy for the brain’s physical form has been demonstrated, until today, it was unknown what types of molecules and organelles were recycled by this mechanism.
The findings of a Lausanne team
This is where the work of a team from the Department of Fundamental Neurosciences of the Faculty of Biology and Medicine (FBM) at UNIL comes into play. “We have developed a new method for purifying autophagosomes from mouse brains and analyzed the cargo they contain,” explains Emmanouela Kallergi, the first author of a study published today in Neuron, conducted in collaboration with the group of Professor Joern Dengjel from the University of Fribourg. The scientists discovered that in neurons and glial cells of the brain, autophagy constantly recycles proteins that aggregate and may lead to diseases, as well as organelles such as mitochondria, the powerhouses of cellular machinery. Additionally, autophagy processes a large number of synaptic proteins essential for the transmission of activity between neurons.
“We also demonstrate that the type of autophagic cargo in the brain changes dynamically during adolescence as the brain matures and at an advanced age, adapting to the needs of each stage of life,” adds Emmanouela Kallergi. “This information is crucial for developing targeted therapeutic strategies that can promote the recycling of specific cellular elements, tailored to the needs of different diseases,” comments the research group leader Vassiliki Nikoletopoulou, an assistant professor at FBM and the last author of the article published in Neuron.
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