Nobel Prize winner Yoshinori Oshumi and Autophagy

Yoshinori Ohsumi


Ohsumi grew up in Japan just after World War II and his father, a professor in engineering, worked at Kyushu University. Ohsumi, being rather successful himself, went on to study Chemistry at the University of Tokyo but he soon realised that he was more interested in molecular biology. After struggling to get good grades in his postgraduate studies, he moved to The Rockefeller University in New York where he pursued a postdoctoral position and this was where he first studied yeast cells which is what he has done his research on ever since.


He now has his own lab and is a professor at the Tokyo Institute of Technology. His primary research interest is in autophagy. His work on autophagy has been pivotal in modern day science — he, alongside his students at his lab, found the majority of pathways and proteins used in autophagy. He also showed that proteins which could sense a cell’s metabolic state were involved in regulating the process. His groundbreaking discoveries were recognised when he won a Nobel Prize in medicine in 2016.

Autophagy


Autophagy is a cell process which takes place within eukaryotes to break down and recycle cell components. The process involves autophagosomes within cells capturing the relevant cell components and transporting them to lysosomes or the vacuole via the cytoskeleton where the contents of the autophagosome is released and broken down.


The vacuole is an organelle primarily associated with plants and yeast cells but smaller, non permanent vacuoles can also be found in animals too. A vesicle is an example of a vacuole. Vacuoles can be viewed under a light microscope which was important in Ohsumi’s work as it meant that he was able to watch the process occurring in living cells in real time.


Cell degradation was known to take place in the vacuole prior to Ohsumi’s work, however, it was unclear how the process actually worked. Ohsumi was able to starve cells (put the cells in a serum lacking nutrients necessary for cells to survive and replicate) and watched what happened under a microscope. He observed that after just 30 minutes of starvation, a stock of vesicles had built up in the vacuole. He then used an electron microscope to see the formation of autophagosomes and vacuole fusion at a higher resolution.


Autophagosomes are a double-membrane vesicle which form on demand so are relatively transient. This is dissimilar from most organelles which exist fairly stably throughout a cell’s lifetime. However, being able to form on demand allows autophagosomes to be produced very rapidly to meet high demand. Autophagosomes are produced by a membrane reorganisation within a cell. A ‘cup-shaped double-membrane sac’ known as the isolation membrane or phagophore appears in the cytoplasm. This can grow rapidly and then seal to form a complete vesicle known as an autophagosome. This process takes as little as 4 minutes in yeast cells and 5-10 minutes in mammals.


The autophagosome is able to fuse to the vacuole in yeast or a lysosome in mammals to form an autolysosome. The inner membrane and the contents of the vesicle is hydrolysed by enzymes within the lysosome resulting in their degradation. This process is used for all kinds of substances from mitochondria all the way to proteins and pathogens.


The broken down materials are then either repaired, reused or used as a source of energy.


(Photo from verywellhealth)

Diet

Nowadays autophagy has even found its place in diet culture. There is a type of fasting known as ‘autophagy fasting’ which involves trying to stimulate rapid autophagy in order to achieve weight loss. It is done by starving the body of necessary nutrients through exercise, fasting and restricting calorie intake. Although research has suggested that these methods can induce autophagy, it puts cells under stress and can cause cell death which is dangerous if this happens excessively. Furthermore, it is difficult to predict which cells will be targeted by autophagy as it may well not be fat cells. The research in this area is still quite limited and so it is unclear what the actual effects are of fasting, whether this does cause autophagy and whether autophagy actually can cause weight loss.


1. Yoshinori Ohsumi

2. Yoshinori Ohsumi

3. Autophagy fasting

4. Autophagy fasting

5. Autophagy in cancer

6. Photo

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