Don W. Fawcett/Science Source, colorization by Mary Martin
Healthy cells must do a good bit of housekeeping. If they didn’t, they soon would be clogged with old, broken or unneeded materials — what most people would think of as trash. Cells clean out their trash through a process that biologists call autophagy (Aw-TOF-uh-gee). But how it worked remained a mystery until a Japanese cell biologist did a lot of probing. What he uncovered won him the 2016 Nobel Prize for physiology or medicine.
The award was announced on October 3.
Cell biologist Yoshinori Ohsumi’s work falls into the category of physiology. That’s the science of understanding how biological parts work. His studies over the years, most recently at the Tokyo Institute of Technology in Japan, have focused on what happens to cells faced with starvation. Rather than give up and die, cells will begin to cannibalize parts they don’t need. Then they’ll recycle — eat or otherwise reuse — those unneeded parts.
But starvation is far from the only motivation for this autophagy, Ohsumi showed. Even healthy cells make use of this process to rid themselves of trash.
Too little recycling can cause cellular trash to build up. That can lead to brain disorders, such as Alzheimer’s and Parkinson’s diseases. Scientists have linked excess recycling, in contrast, with cancer.
“It’s so exciting that Ohsumi has received the Nobel Prize, which he no question deserved,” says Jennifer Lippincott-Schwartz. She’s a biologist with the Howard Hughes Medical Institute. She works at its Janelia Research Campus in Ashburn, Va. This year’s winner “set the framework for an entire new field in cell biology,” she says.
Indeed, Ohsumi‘s discoveries helped reveal the workings of a basic process that underlies biology, notes Maria Masucci. A biologist with the Karolinska Institute, near Stockholm, Sweden, she spoke during a news briefing on October 3. “There is growing hope,” she says, “that this knowledge will lead to the development of new strategies for the treatment of many human diseases.”
Tackling the largely unstudied process
Scientists got their first glimpse of autophagy in the 1960s. This was shortly after the discovery of a pouch within cells known as a lysosome (LY-soh-sohm). It acts as a garbage disposal, grinding fats and proteins and sugars into their basic building blocks. (This discovery would lead to a Nobel Prize in 1974 for Belgian scientist Christian de Duve.)
Researchers had observed lysosomes stuffed with big chunks of cellular wastes. But they also had observed another mystery pouch. Its role seemed to be that of a garbage truck taking those wastes to the lysosome for disposal.
Somehow, the cell had devised a way to consume large parts of itself. De Duve dubbed the process autophagy, from the Greek words for “self” and “to eat.” But for the next 30 years, how it worked remained pretty much a mystery.
“The machinery was unknown,” recalls Juleen Zierath, a Karolinska Institute physiologist. In fact, she notes, “How the system was working was unknown, and whether or not it was involved in disease was also unknown.”
That all changed in the 1990s. It was then that Ohsumi decided to study autophagy in a single-celled organism. He chose baker’s yeast, those microbes responsible for making bread rise. Studying the waste-treatment process in these cells was tricky. That’s partly because it happened so quickly. So Ohsumi bred special strains of yeast. They were not able to break down proteins in their cellular garbage disposals — pouches known as vacuoles (VAK-yoo-oles).
“He reasoned that if he could stop the degradation process, he could see an accumulation of the autophagy machinery in these cells,” Zierath explains.
And it worked.
When he starved these yeast cells, the “self-eating” machinery kicked into gear (presumably to scrounge up food for the cells). But because the garbage disposals were defective, the recycling machinery piled up in the vacuoles. In no time, they swelled like balloons stuffed with sand. Ohsumi could see the bulging, packed bags clearly under a microscope.
His team described this in a 1992 paper in the Journal of Cell Biology.
This opened a world of insights
The new technique let Ohsumi study the process in detail. Within about a year, he discovered as many as 15 genes needed for the cell-recycling machinery to work. Later, Ohsumi and others examined the proteins that these genes had instructed their host cells to make. From this information, the scientists began to figure out how the components of the “bulk waste” bag came together — and then fused with the lysosome.
The work revealed something new about the cell’s garbage centers, Zierath says. Before Ohsumi, biologists had assumed those lysosomes were little more than a trash dump, she notes. “But what he showed was that it wasn’t a waste dump. It was a recycling plant.”
Later, Ohsumi and his coworkers studied autophagy in animal cells and realized that the process played a key maintenance role in all kinds of cells — even those of mammals. Ohsumi “found a pathway that has its counterparts in all cells that have a nucleus,” says 2013 Nobel laureate Randy Schekman. He’s a cell biologist at the University of California, Berkeley. “Virtually every corner of the cell is touched by the autophagic process.”
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Since Ohsumi’s discoveries, research on autophagy has exploded, says Lippincott-Schwartz. “It’s an amazing system that every year becomes more and more fascinating.”
Ohsumi, 71, is still an active researcher. He received the call from the Nobel committee while he was at his lab in Japan. About his work, he said, “It was lucky. Yeast was a very good system, and autophagy was a very good topic.”
Still, he added in an interview with a Nobel representative, “we have so many questions. Even now we have more questions than when I started.”
Ohsumi will receive a medal and cash award of 8 million Swedish kronor (or about $934,000) at a December 10 ceremony in Stockholm. The award is named for Alfred Nobel. Best known as the inventor of dynamite, Nobel was a wealthy man when he died on December 10, 1896. In his will, he left much of his fortune to create prizes to those who have done their best for humanity in the fields of physics, chemistry, physiology or medicine, literature and peace.
(for more about Power Words, click here)
autophagy A normal trash-processing activity of cells. It allows cells to breakdown and recycle wastes. In times of stress, even starvation, it allows cells to reuse some of its unneeded materials to sustain life.
biology The study of living things. The scientists who study them are known as biologists.
cancer Any of more than 100 different diseases, each characterized by the rapid, uncontrolled growth of abnormal cells. The development and growth of cancers, also known as malignancies, can lead to tumors, pain and death.
cell The smallest structural and functional unit of an organism. Typically too small to see with the naked eye, it consists of watery fluid surrounded by a membrane or wall. Animals are made of anywhere from thousands to trillions of cells, depending on their size. Some organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.
development (in biology) The growth of an organism from conception through adulthood, often undergoing changes in chemistry, size and sometimes even shape.
disorder (in medicine) A condition where the body does not work appropriately, leading to what might be viewed as an illness. This term can sometimes be used interchangeably with disease.
fat A natural oily or greasy substance occurring in animal bodies, especially when deposited as a layer under the skin or around certain organs. Fat’s primary role is as an energy reserve. Fat is also a vital nutrient, though it can be harmful to one’s health if consumed in excess amounts.
gene (adj. genetic) A segment of DNA that codes, or holds instructions, for producing a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.
insight The ability to gain an accurate and deep understanding of a situation just by thinking about it, instead of working out a solution through experimentation.
journal (in science) A publication in which scientists share their research findings with the public. Some journals publish papers from all fields of science, technology, engineering and math, while others are specific to a single subject. The best journals are peer-reviewed: They send out all submitted articles to outside experts to be read and critiqued. The goal, here, is to prevent the publication of mistakes, fraud or sloppy work.
lysosome A major structure within cells that is surrounded by a membrane. It's interior liquid is acidic and contains enzymes that can be used to break down (digest) proteins and other types of molecular trash — materials for which the cell no longer has any need.
microbe Short for microorganism . A living thing that is too small to see with the unaided eye, including bacteria, some fungi and many other organisms such as amoebas. Most consist of a single cell.
microscope An instrument used to view objects, like bacteria, or the single cells of plants or animals, that are too small to be visible to the unaided eye.
National Institutes of Health (or NIH) This is the largest biomedical research organization in the world. A part of the U.S. government, it consists of 21 separate institutes — such as the National Cancer Institute and the National Human Genome Research Institute — and six additional centers. Most are located on a 300-acre facility in Bethesda, Md., a campus containing 75 buildings. The institutes employ nearly 6,000 scientists and provide research funding to more than 300,000 additional researchers working at more than 2,500 other institutions around the world.
nucleus Plural is nuclei. (in biology) A dense structure present in many cells. Typically a single rounded structure encased within a membrane, the nucleus contains the genetic information.
organism Any living thing, from elephants and plants to bacteria and other types of single-celled life.
Parkinson’s disease A disease of the brain and nervous system that causes tremors and affects movement, memory and mood.
physiology The branch of biology that deals with the everyday functions of living organisms and how their parts function. Scientists who work in this field are known as physiologists.
proteins Compounds made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. The hemoglobin in blood and the antibodies that attempt to fight infections are among the better-known, stand-alone proteins. Medicines frequently work by latching onto proteins.
recycle To find new uses for something — or parts of something — that might otherwise be discarded, or treated as waste.
strain (in biology) Organisms that belong to the same species that share some small but definable characteristics. For example, biologists breed certain strains of mice that may have a particular susceptibility to disease. Certain bacteria or viruses may develop one or more mutations that turn them into a strain that is immune to the ordinarily lethal effect of one or more drugs.
vacuole A large compartment in a cell.
waste Any materials that are left over from biological or other systems that have no value, so they can be disposed of as trash or recycled for some new use.
yeast One-celled fungi that can ferment carbohydrates (like sugars), producing carbon dioxide and alcohol. They also play a pivotal role in making many baked products rise.
Journal: H. Nakatogawa . . . and Y. Ohsumi. Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nature Reviews Molecular Cell Biology. Vol. 10, July 2009, p. 458. doi: 10.1038/nrm2708
Journal: N. Mizushima, . . . and Y. Ohsumi. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Molecular Biology of the Cell. Vol. 15, December 29, 2003, p. 1101. doi: 10.1091/mbc.E03-09-0704.
Journal: Y. Ohsumi. Molecular dissection of autophagy: two ubiquitin-like systems. Nature Reviews Molecular Cell Biology. Vol. 2, March 2001, p. 211. doi:10.1038/35056522.
Journal: K. Takeshige et al. Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. The Journal of Cell Biology. Vol. 119, October 15, 1992, p. 301. doi: 10.1083/jcb.119.2.301.