An article from University of Oslo
Self-eating keeps us healthy
Right at this very moment, some of our cells are eating themselves. A detailed understanding of this process may be the key to extending our lives.
University of Oslo
Our cells contain many different kinds of waste. For example damaged or old organelles.
If these are not removed and broken down by autophagy, it could lead to cancer and dementia.
Cellular waste management system
“We can envisage the cell as a busy town,” says Professor Anne Simonsen. She is a professor and group leader at the Institute of Basic Medical Sciences at the University of Oslo in Norway.
“For the town to function optimally, it needs to efficiently get rid of waste, to recycle it into new building material and use it for energy production.”
Simonsen and her research group have previously shown that autophagy is important to prevent misfolded proteins from clumping. An accumulation of this kind can lead to Alzheimer’s disease as well as illnesses such as Parkinson’s disease and Huntington’s disease. Researchers have identified several proteins that can bind to such misfolded disease-associated proteins and label them for breakdown through autophagy.
Their most recent findings enhance our understanding of this part of the autophagy process, and might prove significant for developing medication against dementia.
Reversing cancer and dementia?
“We have previously shown that the ALFY protein is important in the process, but until now we have not understood exactly why,” says Simonsen.
In their most recent paper, the research group shows that the protein ALFY is necessary for initiating the autophagy process. If ALFY is removed, the autophagy membrane will not be recruited. As a consequence, misfolded and clumped proteins will not be removed by autophagy, resulting in the death of nerve cells and dementia.
Experiments on the fruit fly Drosophila have revealed that these flies also get dementia if their version of ALFY is removed. Additionally, it has been shown that increased levels of ALFY in these flies can prevent the accumulation of misfolded proteins.
“We hope our studies can help enhance our understanding of the cellular processes that cause cancer and dementia,” Simonsen says.
“And that in the long term we will be able to develop medicines that may prevent or even reverse these diseases, possibly by increasing the production or the effect of ALFY.”
Recycling by self-eating
The word autophagy is derived from Greek and means self-eating. A common explanation of the cells’ waste management system is that our cells eat themselves.
Simply put, this process implies that the cell breaks down its own waste and uses the remains as new building material. A membrane closes around the waste in the cell and forms a unit that is carried to the cell’s waste station where it is broken down. The remaining products from this decomposition are recycled as building material or utilized in energy production for the cell.
The self-eating process is both normal and necessary, and occurs in all our cells all the time.
Extending our lives
The recycling of material that takes place through autophagy contributes in prolonging the lifetime of the cells. Professor Simonsen and her research group have previously shown that a higher level of autophagy can also extend the life of an organism, in this case the fruit fly Drosophila.
“We know that autophagy is initiated and increased by hunger, and there are grounds to believe that increased autophagy is important for the life-extending effect of so-called ‘caloric restriction’ and ‘intermittent fasting’, which are key factors of the popular 5:2 diet,” says Simonsen.
This is primarily explained by the fact that the clean-up provided by autophagy protects us from cancer and other lifestyle diseases.
Too much can be harmful
If it is true that a lack of autophagy cause disease, why can we not just accelerate the autophagy process?
“Studies have shown that in some cases, too much autophagy can be harmful, for example for certain types and stages of cancer,” Simonsen explains.
Consequently, the researchers need to understand the molecular mechanisms involved in the various forms of autophagy in different types of cells in order to manipulate autophagy therapeutically.
“Our research therefore focuses on the basic questions of autophagy: How is the membrane formed? How is the waste recognized? How is the process regulated?”
Read the Norwegian version of this article at forskning.no
- Structural determinants in GABARAP required for the selective binding and recruitment of ALFY to LC3B-positive structures..EMBO Rep. May 1;15(5):557-65