Autophagy grabs Nobel Prize for medicine: All you need to know about pioneering work on 'self-eating' cells!

Zee Media Bureau

New Delhi: The 2016 Nobel Prize in Medicine or Physiology recognizes the pioneering work of Yoshinori Ohsumi, a Japanese scientist, for explaining the recycling system of human cells. He discovered and elucidated mechanisms underlying autophagy, a fundamental process for degrading and recycling cellular components.

What is autophagy mechanism?

The word autophagy is actually a combination of two Greek words- auto meaning "self," and phagein, meaning "to eat". Thus, autophagy means 'self-eating'. This biological concept was originated in 1960 when researchers first observed that the cell could destroy its own contents by enclosing it in membranes, forming sack-like vesicles that were transported to a recycling compartment, called the lysosome, for degradation.

In 1950's scientists discovered that cell contained specialized compartments, with enzymes that digest proteins, carbohydrates and lipids. These specialized compartments called lysosome functions as a workstation for degradation of cellular constituents. And during 1970's and 1980's, researchers explained the in-depth working of a system used to degrade proteins.

Professor Oshumi's experiments on autophagy:

As per Nobel Prize website, Yoshinori Ohsumi had been active in various research areas, but upon starting his own lab in 1988, he focused his efforts on protein degradation in the vacuole, an organelle that corresponds to the lysosome in human cells. At that time he used yeast cells as a model of human cells. But while experimenting he faced a major challenge; yeast cells are small and their inner structures are not easily distinguished under the microscope and thus he was uncertain whether autophagy even existed in this organism.

Ohsumi reasoned that if he could disrupt the degradation process in the vacuole while the process of autophagy was active, then autophagosomes should accumulate within the vacuole and become visible under the microscope. He therefore cultured mutated yeast lacking vacuolar degradation enzymes and simultaneously stimulated autophagy by starving the cells. The results were striking! Within hours, the vacuoles were filled with small vesicles that had not been degraded. The vesicles were autophagosomes and Ohsumi's experiment proved that authophagy exists in yeast cells. But even more importantly, he now had a method to identify and characterize key genes involved this process. This was a major break-through and Ohsumi published the results in 1992.

Within a year of his discovery of autophagy in yeast, Professor Oshumi had identified the first genes essential for autophagy. After this successful experiment he studied thousands of yeast mutants and identified 15 genes that are essential for autophagy. Subsequently, he characterised the proteins encoded by these genes according to their function. The results showed that autophagy is controlled by a cascade of proteins and protein complexes, each regulating a distinct stage of autophagosome initiation and formation.