How cells digest themselves

Yoshinori Ohsumi, of the Tokyo Institute of Technology, was awarded science's most prestigious award for "his discoveries of mechanisms for autophagy," the Nobel Committee for Physiology or Medicine announced in Stockholm on Monday October 3rd.

"The work of Yoshinori Ohsumi dramatically transformed the understanding of this vital cellular process," the committee announced.

In most years, two or three scientists have to share the Nobel Prize between them because their work has been similarly essential to drive a research field forward.

'The key figure'

Volker Haucke, the director of the Leibniz Institute for Molecular Pharmacology in Berlin, told DW that the committee made the right decision.

"Oshumi is the key figure in unraveling this pathway, with studies that started in the early 1980s," Haucke said. "He is the person who started to delineate the process of autophagy in yeast at a time when researchers worldwide hardly knew autophagy even existed."

Monda's announcement was no surprise to many scientists in Oshumi's research field. "Everyone reckoned that it was Oshumi's turn," said Thomas Wollert, of the Max Planck Institute of Biochemistry.

Toxic cell material

Autophagy, a Greek compound meaning "self-eating," was coined in the 1960s by the Belgian biochemist Christian de Duve. He had observed the phenomenon for the first time in liver tissue when he discovered the lysosome - the recycling compartment of cells - for which he was awarded the Nobel Prize in Physiology or Medicine in 1974.

Cells use this process to destroy their contents when they have no more use for them.

"Autophagy is the prime pathway that takes care of damaged proteins or organelles that accumulate over time," Leibniz's Haucke said. 

The Planck Insitute's Wollert calls it a recycling system that enables cells to break down those unwanted parts into their components and use them again for other purposes. The process is essential for cellular health, he said.

"For example, when mitochondria - the cells' power plants - are damaged, they can release toxic free radicals," Wollert said. "So the cells have to get rid of those damaged mitochondria as soon as possible."

By enclosing those organelles in membranes and forming sacklike vehicles around them, the cell transports them to their lysosomes, where the cell parts are degraded into their components.

Hunger stimulates self-destruction

By eliminating damaged proteins, autophagy is critical for counteracting the negative consequences of aging. Even more important, Wollert said, autophagy enables humans to cope with scarce food sources - in other words: starvation.

"In times of hunger, a cell will enclose part of their cytoplasm, digest it and thus regain important nutrients," Wollert said. "This way, a cell can uphold its vital functions."

Wollert compares it to what some people call going on a diet. With less food than usual or none at all, people get thinner but stay alive.

"Autophagy starts every time you have not eaten for more than 12 hours," said Rupert Langer, of the Institute of Pathology at the University of Bern. If researchers shut down the process of autophagy in lab animals and then don't feed them for a while, those animals die quickly, he added: "They can't cope with the stress of starvation."

Dedicated to autophagy

For decades following de Duve's prize, no other researcher had shown as much interest in autophagy as Ohsumi.

"He dedicated his life to autophagy," Wollert says.

In the early 1990s, Ohsumi used a simple organism - baker's yeast - to identify the genes essential for the process. 

"In a series of elegant subsequent studies, he cloned several of these genes in yeast and mammalian cells and elucidated the function of the encoded proteins," the Nobel Committee announced.

Ohsumi published his results in 1992. 

"When it became clear that the pathway is of fundamental importance, many researchers became interested," Haucke said. "There are thousands of publications on autophagy each year nowadays."  

The increased interest arose when it became apparent that autophagy happens in human cells as well and that the process is involved in causing cancer and neurodegenerative diseases.

Born in 1945, Ohsumi continues to work as a professor at the Tokyo Institute of Technology. He is about to retire and is in the process of scaling down his research group, Wollert said.

"But," Wollert said, "maybe this Nobel prize will motivate him to continue on his research after all."