This year the Nobel Prize in Physiology or Medicine was awarded to Yoshinori Ohsumi, a Japanese biologist who discovered autophagy—the process used by cells to clean and recycle their components. Group Leader Antonio Zorzano studies autophagy in his research at IRB Barcelona, and explains why it is such a key discovery in an interview published in La Vanguardia.
What is autophagy and how does it work?
Autophagy is a process that takes place in all cells, from yeast to human cells. It’s responsible for renewing cell machinery and it’s a perfect recycling system: everything that is damaged or that doesn’t work properly is broken down. Basic molecules are regenerated so that new components can be synthesised. It’s a system that recognises cell organelles that are not working. The defective parts are covered by a double membrane to form a vesicle known as an autophagosome. Next, this vesicle fuses to a lysosome, an organelle that holds an arsenal of enzymes capable of breaking down organic molecules into their most basic components, such as amino acids and monosaccharides.
Why is this process important?
This process is crucial for correct cell function. For example, it allows muscle cells to contract and the pancreas to secrete insulin. Cells need autophagy to degrade deficient components and regenerate new ones.
When autophagy doesn't work properly, the cell often dies. In the pluricellular world, in people and animals, the impairment of autophagy can lead to diseases. Today, the enormous relevance of autophagy lies in its association with serious human diseases, such as type 2 diabetes, obesity, cancer and neurodegenerative conditions like Parkinson’s disease. We hope that studies into autophagy will help to find treatments against these diseases. In fact, leading pharmaceutical companies have started projects to identify compounds that can modulate autophagic activity.
What is the story behind the discovery of this process?
Scientists first start to study autophagy in the 1960s or earlier, and even in the 1990s, our knowledge about autophagy was still quite inaccurate. Ohsumi was able to identify the mechanisms of autophagy in a cell as simple as yeast. It turned out that the genes he discovered in yeast are also present in humans. How lucky is that? This led Ohsumi to map autophagic genes both in yeast and in humans.
How did you get into studying autophagy?
In my case, results led me to it. Our group studies why obesity and type 2 diabetes occur and why some people are more susceptible to these conditions than others. Some years ago we cloned a gene that is deregulated in the muscle of diabetic patients, and it turned out that it was an autophagic gene. For the last ten years, we have been studying how this gene participates in cell metabolism.