Professor Rachan Oh, a Japanese professor who won the Nobel Prize in Physiology or Medicine in 2016, has made significant contributions to modern medicine through his research on the autophagy mechanism. Autophagy breaks down unnecessary substances in cells to help metabolize them, and it plays a key role in addressing Parkinson’s disease and other age-related issues. His research has provided important clues for disease treatment and anti-aging research in this field.
On October 3, 2016, Professor Emeritus of the Tokyo Institute of Technology, Japan, was awarded the Nobel Prize in Physiology or Medicine for his discovery of part of the autophagy mechanism. The 25th Japanese Nobel Prize winner in history, Prof. Dai has devoted 50 years to autophagy research. He has already received prestigious awards for his work in this field. He was awarded the Japan Academy of Sciences Prize in 2006, the Kyoto Prize in 2012, the Keio Prize in Medicine in 2015, and the Wally Prize in 2016, further cementing his status as a world-renowned scientist. But what is the significance and meaning of autophagy to the development of modern medicine, and why has the scientific community taken such an interest in autophagy?
As the term autophagy suggests, autophagy is a destructive mechanism that naturally breaks down unnecessary or non-functional cellular components within a cell. In other words, it is a system that recycles cellular components that the cell does not need in order to survive. It plays a key role in how cells metabolize and sustain life. When cellular organelles, such as mitochondria, which produce energy, or liposomes, which store and transport substances, become damaged and unusable or less efficient, autophagosomes and other cellular organelles called lysosomes break them down. Our cells have many membrane structures with different functions, but all of them, including the cell membrane, are composed of the same materials and in the same way, which makes the exchange of materials between them very flexible. Autophagosomes and lysosomes are two of these membranous structures, and when autophagosomes engulf aged and obsolete components, they combine with lysosomes that contain digestive enzymes to digest them. An easy analogy to understand is that autophagosomes are like trucks that haul garbage, and lysosomes are like incinerators that burn the garbage.
In 1988, when Professor Dai Liangxuan had his own lab, he began to focus on proteolysis in the vacuole, the lysosomal equivalent of the endoplasmic reticulum in human cells. He studied autophagy in Saccharomyces cerevisiae cells, which are easy to study and often used as a proxy for human cells. Yeast are particularly useful for sequencing the genes that control specific intracellular activities. However, Dai faced a challenge: yeast cells are too small to see if autophagy is even occurring inside the cell. Dr. Dai hypothesized that by artificially interfering with the degradation process in the lysosome, autophagosomes would accumulate around the lysosome, which would be easier to observe under a microscope. To put this into practice, he mutated a proteolytic gene in the yeast to prevent protein degradation in the lysosomes and cut off the supply of nutrients to the yeast, thus triggering autophagy. As a result, he was able to observe that the lysosomes were filled with small vesicles corresponding to autophagosomes, proving that autophagy was occurring in the yeast cells. This discovery marked a major turning point in the study of autophagy, and led to Prof. Dai’s successful sequencing of the genes involved in the autophagic process using yeast. This has had an important impact on many subsequent studies of autophagy and has led to major advances in modern physiological medicine.
Autophagy breaks down unnecessary substances in the cell to increase the efficiency of metabolism and replenish nutrient deficiencies. Since most of the unnecessary materials in cells are aging organelles, understanding autophagy plays an important role in finding solutions to human aging and its problems. In particular, autophagy holds the key to treating Parkinson’s disease. Parkinson’s disease is caused by excessive nitric oxide binding to Parkin proteins, which prevents them from functioning properly, and it has been shown that autophagy does not occur when Parkin proteins are inactive. “Professor Dai’s research has enabled the understanding and analysis of autophagy at the genetic level, which has brought mankind one step closer to solving various autophagy-related diseases such as Parkinson’s disease, and is considered a major contribution to the advancement of human physiology.
Autophagy research is not limited to disease treatment. The process by which autophagy removes unnecessary components from cells also provides important clues to solving age-related problems that occur throughout the body. For example, if unwanted materials in cells are not removed, they can cause cellular deterioration and accelerate aging throughout the body. Given that the autophagy mechanism contributes to inhibiting this aging and maintaining cellular health, it is expected to play an important role in future anti-aging and life extension research. As such, autophagy is a key mechanism of survival and regeneration at the cellular level, making it a powerful tool for responding to various challenges facing modern medicine. “Prof. Dai Liangzhen’s research has contributed greatly to the realization of this potential, and his Nobel Prize is a global recognition of his contributions.
