Medicine Nobel prize for autophagy breakthroughs


Rebecca Pool

Monday, October 3, 2016 - 14:45
Image: Professor Yoshinori Ohsumi is a Japanese cell biologist specializing in autophagy.
Yoshinori Ohsumi from the Tokyo Institute of Technology has won the Nobel prize in medicine for discoveries on autophagy.
In a series of brilliant experiments in the early 1990s, Ohsumi identified the genes essential to this process of cell detoxification and repair.
He went on to elucidate the underlying mechanisms for autophagy in yeast, revealing that similar sophisticated machinery is used in human cells.
As Ohsumi said in an interview with Tokyo Tech: "All my research findings started from observations with a microscope. So even now, I always get the students who come to my laboratory to work with a microscope... I want my students to naturally confirm things with their own eyes and hopefully make new discoveries with their own eyes too."
Ohsumi's breakthrough research was published in Wiley journal, FEBS Letters.
Figure 2: In yeast (left panel) a large compartment called the vacuole corresponds to the lysosome in mammalian cells. Ohsumi generated yeast lacking vacuolar degradation enzymes. When these yeast cells were starved, autophagosomes rapidly accumulated in the vacuole (middle panel). His experiment demonstrated that autophagy exists in yeast. As a next step, Ohsumi studied thousands of yeast mutants (right panel) and identified 15 genes that are essential for autophagy. 
While autophagy is the body's internal recycling process, it also helps to keep pathogens at bay, prevents the protein accumulation that can lead to neurodegenerative diseases, arrests cancerous growth, protects against diabetes and more.
To understand this process, Ohsumi began experimenting with baker's years - often used as a model for human cells - at a time when researchers were uncertain that autophagy existed in this organism.
He first cultured mutated strains that lacked vacuolar degradation enzymes, and then used light and later electron microscopy to show that when yeast cells were starved, a key structure in autophagy, autophagosomes, accumulated in the vacuole.
Having demonstrated that autophagy existed in yeast cells, he went onto study thousands of yeast mutants, identifying the genes essential for the process and characterising the proteins encoded by these genes.
His research revealed that autophagy is controlled by a cascade of proteins and protein complexes, each regulating a distinct stage of autophagosome initiation and formation.
Come the 1990s, the research tools required to investigate autophagy in human cells were available and thanks to Ohsumi's ground-breaking work, researchers now know that autophagy controls key physiological functions were cellular components need to be degraded and recycled.
Disrupted autophagy has been linked to Parkinson's disease, type 2 diabetes and other disorders that appear in the elderly.
Mutations in autophagy genes can cause genetic disease while disturbances in the autophagic machinery have been linked to cancer.
Intense research is now ongoing to develop drugs that can target autophagy in various diseases.
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