Japanese cell biologist, Yoshinori Ohsumi, won the 2016 Nobel Prize for Medicine by discovering the process of autophagy by which cells recycle material. It literally means cannibalism — “eating the self”. Cells "eat" their own waste material and breakdown the material to recycle it, either as energy or as building blocks for new structures.
The 71-year-old Ohsumi was born in 1945 and completed his Phd at Tokyo University in 1974. His early career involved quite a few shifts in focus. He started out as a chemist, discovered he couldn't easily get a job and switched to genetics. Then he switched to molecular biology. He remains an emeritus professor at the Tokyo Institute of Technology and is still actively involved in research.
The process of autophagy involves breaking down waste materials and reusing them. It is also an important system for combating diseases. Once an invading virus or bacteria has been destroyed, cells use autophagy for recycling the dead material. Cells also repair damage within themselves by "eating" damaged material and reusing it.
Disruptions of the autophagy process occur in cancers, in ageing, in diabetes and in many neuro-degenerative diseases. Thanks to Ohsumi's work, new drugs that can stimulate autophagy are being studied, and this could mean a better understanding of cancers, and an overall increase in life expectancy. Ohsumi focussed on the yeast cell and worked out many details even as he discovered how important the process was. He identified around 15 genes associated with autophagy and also learnt how to inhibit it. This was pioneering work. Importantly, the autophagy process is quite similar in simple organisms like yeast, and in complex mammals like human beings.
The concept of autophagy was not in itself new. In the 1960s, researchers first observed that the cell could destroy its own contents by enclosing it in membranes, forming little bags (vesicles) that were recycled in a chamber, called the lysosome. This in itself, followed up on a series of prior discoveries. Scientists had discovered the specialised cellular chamber, the lyosome, in the 1950s. This contains enzymes that digest proteins, carbohydrates and fats, for the purpose of recycling. Christian de Duve was awarded the Nobel in 1974 for discovering the lyosome and its purpose.
In the 1960s, further analysis revealed that there was a “transport system” to carry material for recycling to the lyosome. This consisted of sacks called vesicles. De Duve coined the term, autophagy and he called these vesicles, autophagosomes. But nobody figured out the mechanism for actually breaking down large proteins, even though there was research in this field through the 1970s and 1980s.
In a series of experiments in the early 1990s, Ohsumi used yeast to figure out the mechanism and identify the essential genes for autophagy. He later showed that similar methods are used in human cells. He also discovered how this process can be an adaptation to starvation, or a response to infection. In 1988, Ohsumi started examining the process of protein degradation in yeast.
The yeast cell has a chamber called the vacuole, which has a similar purpose to the lysosome. Yeast is relatively easy to study as an organism and it has often aided in the identifying of new genes. But yeast cells are small and Ohsumi was not even sure how he could observe autophagy or indeed, if it occurred at all in yeast.
In a brilliant feat of reasoning, he found a way to disrupt autophagy. He cultured mutated yeast carefully removing some of the enzymes required for autophagy, and, at the same time, he stimulated autophagy process by starving these cultured cells. Very soon, this resulted in creating many autophagosomes, which did not degrade because autophagy was disrupted.
The presence of those autophagosomes proved that autophagy did indeed exist in yeast. It also gave him a way to identify key genes, by culturing new batches of yeast, each with different mutations. The idea was, if genes, key to the process, were inactivated by a given mutation, he would be able to identify those key genes because of the disruption of the process (or autophagy would not start at all).
Over the next two years, Oshumi discovered how this process functioned, identifying 15 genes that regulated various stages in autophagy. The next step was identifying analogous processes in more complex organisms, such as human beings. This was when other researchers also got into the act and an understanding of autophagy rapidly developed. It can provide fuel for energy and building blocks for renewal of cells, and is therefore essential in case of starvation or stress. After infection, autophagy also eliminates the invading bacteria and viruses. It contributes to embryo development and cell differentiation. Cells also use autophagy to eliminate damaged proteins and organelles and this repair is key to combating ageing.
Subsequent research continues to built upon Oshumi's discoveries. Researchers are now looking to develop drugs that can stimulate autophagy in various diseases, where the process is disrupted. This is a new angle for medical research in a field that would probably not exist except for Oshumi's efforts.
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