apanese biologist Yoshinori Ohsumi on Monday won the Nobel Prize in physiology or medicine for seminal work on the fundamental cell process called autophagy, which literally means “self-eating.”
Autophagy, which was discovered in the 1950s, allows cells to recycle their contents rather than simply dispose of proteins and other molecules that they have already used.
The mechanism helps cells destroy invading bacteria and viruses, eliminate damaged proteins, and respond to stresses such as starvation. Disruptions in autophagy have been linked to diseases including Parkinson’s, cancer, and type 2 diabetes.
Ohsumi pinpointed the key genes that drive autophagy and demonstrated that the process is controlled by a cascade of proteins. His central experiments were done in the 1990s, making this another Nobel in which the prize committee has reached back decades for work to honor. The prize money comes out to 95 million Japanese yen, or about $936,000.
“Ohsumi’s discoveries led to a new paradigm in our understanding of how the cell recycles its content,” the Nobel committee said in its citation. “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 [and] … conditions including cancer and neurological disease.”
A number of academic labs and biotechs are working on manipulating autophagy to block tumor growth, reduce heart damage from myocardial ischemia, and suppress viral infections.
There is no dispute that autophagy is a key cellular process, deserving of a Nobel.
But the committee’s decision to award the prize to Ohsumi alone may cause some ripples in the scientific community.
When the crystal-ball gazers at Thomson Reuters made their Nobel predictions in 2013, forecasting that the medicine prize would eventually honor discoveries in autophagy, they named a trio of possible winners: Ohsumi, of the Tokyo Institute of Technology, as well as Daniel J. Klionsky of the University of Michigan and Noboru Mizushima of the University of Tokyo.
Ohsumi’s work builds on the discovery in the 1950s that vesicles inside cells — called autophagosomes — would engulf spent structures such as mitochondria or even bits of cytoplasm and ferry them to what had been considered the cell’s garbage disposal, a structure called the lysosome. In 1988, Ohsumi began studying autophagy in brewer’s yeast, a one-celled organism that is a favorite of biologists because of its relatively simple genetics.
“Nothing was known about what or how cytoplasmic constituents are degraded in the vacuole,” as the lysosome is called in yeast, he told Thomson Reuters in 2013. “When I started my own lab [in 1988], just by myself, I decided work on this subject. … My hope was that the yeast vacuole might become a good system for the study of molecular mechanisms of intracellular protein degradation.”
He discovered that autophagy seemed to occur when the yeast was running out of nutrients: The yeast cells were breaking down their own parts and recycling them to stay alive, allowing them to survive a month or more with little outside sustenance.
Ohsumi discovered that some mutant yeast were terrible at autophagy and died within days. He identified the mutant genes, from a family called Atg’s, in 1992; as he told Thomson Reuters, “identification of these genes evoked a revolutionary change in the research field of autophagy.”
When Mizushima joined his lab, he and Ohsumi together succeeded in identifying the mutant proteins and their interactions. Mizushima created mutant mice that were deficient in autophagy. That helped reveal the key role autophagy plays in normal development: In very early embryos, for instance, autophagy recycles maternal proteins into its own. And when cells are deprived of nutrition, they cannibalize themselves in order to survive.
“I am proud that the molecular studies of mammalian and plant autophagy also originated in my lab,” Ohsumi said in 2013. “Mizushima [and another colleague] so nicely developed excellent progress in mammalian autophagy there.”
Mice whose mutations keep them from autophagy, Mizushima and others also discovered, develop way more tumors than normal mice. And in Parkinson’s disease, cells fail to clear out and recycle defective mitochondria.
That process — autophagy of mitochondria — has been Klionsky’s focus, something that in 2009 led science watchers to call him one of the “leaders of this autophagy revolution.”
Under the terms of Alfred Nobel’s will, up to three laureates can be named for each of the science prizes. But the committee went with Ohsumi alone.
“I assumed that if the committee were to name only one, it would be Ohsumi,” said David Pendlebury of Thomson Reuters, who helps make the company’s Nobel forecasts. Ohsumi is “the pioneer and senior figure, even if Mizushima extended the work in important ways, as did Klionsky to a lesser degree in confirming [their] discoveries.”
The Thomson Reuters selections, he added, are “meant to recognize the important contributions of individuals even if they are not selected in the end for the Nobel Prize, and this is a good example.”
This story has been updated with more information about Ohsumi’s work.