Kimberly Hatfield Freelance Writer GEN

Yoshinori Ohsumi’s Work Has Demonstrated the Significance of Autophagy to Human Health

When Dr. Yoshinori Ohsumi began researching autophagy 27 years ago there were maybe 20 papers published annually on the subject. Today that number is in the thousands largely due to Ohsumi’s paradigm-shifting work that demonstrated the fundamental importance of autophagy in many physiological processes and its significance to human health. Dr. Ohsumi received the 2016 Nobel Prize in Physiology or Medicine for this work.

“Thanks to the work of Yoshinori Ohsumi and many others that followed in his footsteps we now know that autophagy regulates important physiologic functions of the cells and that defects of autophagy are associated with many human diseases,” said Maria Masucci of the Nobel Assembly at the announcement. 


“Self Eating” Mechanism Impacts Human Health

Derived from Greek words meaning self eating, autophagy is about far more than consumption. Autophagy is a powerful degradation and recycling mechanism in cells. It plays an essential role in cell survival. And its dysfunction is linked to several diseases including diabetes mellitus, neurodegenerative disorders, infectious diseases, and cancer.

Dr. Ohsumi was born in Fukuoka, Japan, in 1945 just a few years ahead of dramatic advances in cell biology research. Belgian scientist Christian de Duve, “on a chance discovery,” identified the lysosome in 1955. Further studies revealed that large amounts of cell contents were delivered to the lysosome and broken down, leading Dr. de Duve to coin the term autophagy. Dr. de Duve and two colleagues were awarded the Nobel Prize in 1974 for this work, but many questions remained on the role and mechanism of autophagy.


“Brilliant Experiments”

Dr. Ohsumi studied at the University of Tokyo earning both his bachelor and doctoral degrees. He was initially interested in chemistry and then molecular biology. As a graduate student he studied protein synthesis in E. coli, but was unable to gain traction with his work. He took a postdoc position at Rockefeller University to study in vitro fertilization in mice under Dr. Gerald M. Edelman, also a Nobel Laureate.

“I failed to get any satisfactory results, but learned something in cell biology, and strangely enough I started yeast work in his lab,” Dr. Ohsumi told Sciencewatch.com.

Dr. Ohsumi returned to the University of Tokyo where he eventually set up his own lab studying protein degradation in yeast cell vacuoles. It was his belief that fundamental functions of cells should be conserved from yeast to mammals.

A series of experiments using baker’s yeast that the Nobel committee called “brilliant” helped Dr. Ohsumi identify genes essential for autophagy. He also deciphered the underlying mechanisms of autophagy in yeast and showed that a similar system existed in human cells. 

“One thing I want to say is that I like to observe cells under a microscope,” Dr. Ohsumi told the Journal of Cell Biology in 2012. But yeast’s small cell structures presented a challenge. So he devised a way to amass physical evidence of autophagy with autophagosomes, the membrane-enclosed vesicles responsible for capturing and transporting cellular components.

Working with mutated yeast, he stimulated the autophagy process and at the same time disrupted the degradation process. Evidence accumulated, confirming autophagy in yeast cells and leading to the identification of genes involved in the process.

In 1993, Dr. Ohsumi published his “seminal discovery” of 15 essential yeast autophagy genes in FEBS Letters. He went on to functionally characterize the proteins encoded by these genes.

“Ohsumi and his colleagues were also the first to identify genes that control autophagy in mammalian cells. This allowed the production of research tools that has transformed autophagy into one of the most intensely studied topics of biomedical research,” Masucci said. 


“Still We Have So Many Questions”

Today, autophagy is known to clear intracellular bacteria and viruses after infection, contribute to embryo development, eliminate damaged cell contents that are related to aging, and rapidly respond to stressors like starvation by providing fuel and key building blocks. Disrupted autophagy is linked to several diseases. And mutations in autophagy genes are linked to neurodegenerative diseases, infectious diseases, and cancers.

Dr. Ohsumi was in his lab at the Tokyo Institute of Technology when Nobel committee secretary Professor Thomas Perlmann called with the news. Dr. Ohsumi is the sole recipient of this year’s medicine prize, a distinction shared by only 38 others. The majority, 68 prizes, have been shared by two or three Laureates each year. The Nobel Prize amount for 2016 is eight million Swedish kroner.

His reaction to the news was one of surprise and he emphasized how much work is still to be done. “Still we have so many questions. Even now we have more questions than when I started,” he told Adam Smith, chief scientific officer of Nobel media. 







































 

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