Nobel Prize in Medicine Awarded for Autophagy Discoveries

    Yoshinori Ohsumi, Ph.D., a microbiologist who discovered and elucidated mechanisms underlying the degradation and recycling of cellular components, was named sole winner of the 2016 Nobel Prize in Physiology or Medicine.

    Dr. Ohsumi, a professor at the Tokyo Institute of Technology, was honored for discoveries that shed light on the importance of autophagy in many physiological processes, such as in the adaptation to starvation or response to infection.

    In the early 1990s, Dr. Ohsumi used baker’s yeast to identify genes essential for autophagy, then proceeded to elucidate the underlying mechanisms for autophagy in yeast, showing that a similar process is employed in human cells.

    Dr. Ohsumi’s discoveries “led to a new paradigm in our understanding of how the cell recycles its content,” the Nobel Assembly at Karolinska Institutet in Stockholm stated.

    Dr. Ohsumi was born in 1945 in Fukuoka, Japan, and received his Ph.D. in 1974 from the University of Tokyo. After spending three years at The Rockefeller University, he returned to the University of Tokyo, where he established his research group in 1988.

    Upon starting his own lab, Dr. Ohsumi focused on protein degradation in the vacuole in yeast cells. Because yeast cells are small and their inner structures not easily distinguished under the microscope, he was uncertain whether autophagy even existed in yeast. By disrupting the degradation process in the vacuole while autophagy was active, he reasoned, autophagosomes should accumulate within the vacuole and become visible under the microscope.

    Dr. Ohsumi cultured mutated yeast lacking vacuolar degradation enzymes and simultaneously stimulated autophagy by starving the cells. Within hours, the vacuoles were filled with autophagosomes that had not been degraded, showing that authophagy existed in yeast cells. More importantly, the experiment yielded a method to identify and characterize key genes involved in the process, according to results he published in 1992.

    He followed up by exposing the yeast cells to a chemical that randomly introduced mutations in many genes, then inducing autophagy. Within a year of his discovery of autophagy in yeast, Dr. Ohsumi identified the first genes essential for the process. In later studies, the proteins encoded by these genes were functionally characterized, showing that autophagy was controlled by a cascade of proteins and protein complexes, each regulating a distinct stage of autophagosome initiation and formation.

    Since then, autophagy has been shown to contribute to embryo development and cell differentiation, and to be essential for directing cellular response to starvation and other types of stress. It also is important for eliminating invading intracellular bacteria and viruses and for eliminating damaged proteins and organelles. Disrupted autophagy has been linked to Parkinson’s disease, type 2 diabetes, and other disorders in elderly people, and mutations in autophagy genes can cause genetic disease. Disturbances in the autophagic mechanism have been linked to cancer.

    “Autophagy has been known for over 50 years but its fundamental importance in physiology and medicine was only recognized after Yoshinori Ohsumi’s paradigm-shifting research in the 1990’s,” the Nobel Assembly added.