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Insights into human cell recycling: Research team led by Roberto Covino FIAS Fellow and scientist at LOEWE-CMMS achieves major breakthrough in understanding autophagy
Cells have a sophisticated "recycling system" called autophagy. This term from ancient Greek means "self-consuming" and is a complex process. All cellular components - such as small molecules, sugars, individual proteins, lipids - are organized in an enormously complex choreography that is necessary for the proper functioning of the cell and ultimately for the health and survival of the entire organism. Sometimes parts of this choreography become damaged - such as a protein complex or a membrane - and the cell must eliminate them before they interfere with its normal function. Or a cell suffers from nutrient deficiency, so it must use and recycle existing molecules to focus on essential activities. Autophagy is also activated in these situations.
Autophagy relies on the interaction of numerous regulatory proteins that control the formation of this cellular "garbage disposal". They collect the cell contents intended for recycling - for example, defective proteins - in vesicles called autophagosomes. A crucial role in the formation of these autophagosomes, the structures that encapsulate the material to be degraded, is played by the protein ATG3.
The research team led by FIAS Fellow Roberto Covino, who is also a scientist at LOEWE-CCMS, focused their studies on a specific side chain of the ATG3 protein, the amphipathic α-helix (AHATG3). They found that this side chain has unique biophysical properties: These properties allow it to interact with membranes in a tightly controlled manner. And they are essential for the protein's function in autophagy.
Using advanced computational techniques combined with cell biology experiments, the researchers simulated and observed the dynamics of the ATG3 protein and its interaction with membranes during the autophagy process. They found that the unique properties of ATG3 are critical for a key step in autophagosome formation.
This deeper understanding of the molecular mechanisms underlying autophagy could have significant implications for developing treatments for diseases associated with impaired autophagy, such as neurodegenerative diseases and cancer.
Publication:
Taki Nishimura, Gianmarco Lazzeri, Noburu Mizushima, Roberto Covino, Sharon A. Tooze, Unique amphipathic α helix drives membrane insertion and enzymatic activity of ATG3.Sci. Adv.9,eadh1281(2023).DOI:10.1126/sciadv.adh1281 
Contact:
Dr. Roberto Covino Frankfurt Institute for Advanced Studies (FIAS), phone: +49 69 798 47659 covino@fias.uni-frankfurt.de