Medicine Nobel honors research on how cells eat themselves
This year's Nobel Prize in Physiology or Medicine has been awarded to Yoshinori Ohsumi, a cell biologist at the Tokyo Institute of Technology’s Frontier Research Center, for his work on autophagy, the process in which cells degrade and recycle cellular components. Understanding autophagy is key to unlocking treatments for diseases like cancer, diabetes, and Huntington disease.
"Ohsumi's discoveries led to a new paradigm in our understanding of how the cell recycles its content," a press release by the Nobel Assembly at the Karolinska Institute (KI) in Stockholm says. "His discoveries opened the path to understanding the fundamental importance of autophagy in many physiological processes, such as in the adaptation to starvation or response to infection. Mutations in autophagy genes can cause disease, and the autophagic process is involved in several conditions including cancer and neurological disease."
The path to resolve the puzzle started in the 1950s and 1960s when researchers recognized that some animal cells use autophagy to recycle proteins and other cellular machinery. It was observed that the process was especially active when the cell was under stress, for example when cells are in short supply of nutrients or when the organism was fighting off an infection. But the detailed mechanisms involved in the process, even the type of cells that adopts the method, remains unclear.
Ohsumi and his colleagues set out to explore whether yeast, a single-celled organism that nevertheless uses many of the same biochemical processes as animal cells, could help answer some of the outstanding questions. "I thought of trying something others weren't working on, so I started research into yeast," Ohsumi explained at his press conference. Ohsumi developed strains of yeast that lacked key enzymes suspected of playing a role in autophagy, hoping to see what happened to the cells when the process didn’t work as it should. When they starved the yeast, the scientists found that the cells developed unusually large vacuoles, the cellular garbage dumps that collect materials to be recycled. Usually yeast vacuoles were too small to see under the light microscope, but in the mutant yeast, they grew so large they were easy to observe.
Ohsumi then used chemicals to induce more mutations in the yeast strains, looking for cells that failed to form visible vacuoles even when they were starving. Such cells, he reasoned, lacked genes that were important for autophagy to work properly. In a key paper published in FEBS Letters in 1993, Ohsumi and and his team identified 15 essential genes involved in the process. Further studies showed that very similar genes controlled the process in animal and human cells, and also helped piece together how the genes work together to keep the cell’s recycling centers running.
Since then, Ohsumi and others have shown that autophagy plays a crucial role in embryo development, cell differentiation, and the immune system. A breakdown in autophagy can lead to a wide variety of diseases, including cancer, diabetes, and Huntington disease. A healthy autophagy system is correlated with longevity, and a faulty one can accelerate symptoms of aging.
Ohsumi, who will collect 8 million Swedish kronor (US$940,000) for the Nobel prize, also won the ¥50-million (US$626,000) Kyoto Prize in basic sciences in 2012 for his autophagy work. Others have made key contributions to the field, and were considered to be contenders for a share of a Nobel. Biochemist Michael Thumm of the University Medical Center Göttingen in Germany, for example, also discovered autophagy genes, as did cell biologist Daniel Klionsky of the University of Michigan in Ann Arbor.
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