Science News - March 26, 2011

mechanics that keep autophagy in balance. Recent work, for example, shows that faulty versions of a gene that helps spark autophagy can make people more susceptible to tuberculosis. While boosting autophagy can help prevent cancer, researchers have found that once cancerous, cells can hijack the self-eating mechanism, a twist that suggests reining in autophagy may keep tumors at bay.

And for a number of neurodegenerative diseases — including Parkinson’s and Alzheimer’s — ne w studies show that cells can’t quite get their toxic innards down. In some cases, treating these diseases may be a matter of encouraging autophagy, while others may require a tightening of the self-cannibalizing belt.

To keep things tidy, nerve cells (red)
nibble away at themselves via Pac-Man–
like structures (green and yellow). DININGIN

How the right
amount of cellular
self-cannibalism can
keep you healthy

By Tina Hesman Saey

There’s a little Hannibal Lecter in all of us. But while the famous can- nibal dined on chunks of his enemies and friends, most people stick to gnawing on themselves at a microscopic level. In fact, the cells of organisms from yeast to humans regularly engage in self-cannibalism. Cells chew on bits of their cytoplasm — the jellylike substance that fills their bellies — and dine on their own internal organs, although usually without the fava beans and Chianti.

It may sound macabre, but gorging on one’s own innards, a process called autophagy, is a means of self-preservation, cleansing and stress management.

“It has become evident that it is really an essential or vital function,” says Fulvio Reggiori, a cell biologist at the

University Medical Center Utrecht in the Netherlands.

A munch here gets rid of garbage that might otherwise clog the system. A nibble there rids cells of malfunctioning parts. One chomp disposes of invading microbes. In lean times, all that stands between a cell and starvation may be the ability to bite off and recycle bits of itself. And in the last decade or so it has become clear that self-eating can also make the difference between health and disease.

“Too much or too little autophagy is a problem,” says Daniel Klionsky, a cell biologist at the University of Michigan in Ann Arbor.

A cell that bites off more than it can chew can kill itself, Klionsky says. A few rare genetic diseases are linked to an excess of unsuccessful autophagy: The muscles of people with Danon disease, Pompe disease and X-linked myopathy can become weak after filling up with Pac-Man–like structures that put the bite on the cell’s insides but can’t finish digesting.

Not enough autophagy can also lead to disease. Most notably, a cell that can’t clean itself up can turn cancerous.

With their sights on fighting disease, scientists are now uncovering the

Cellular dinnertime

Scientists have known since the early 1960s that autophagy happens. But until a decade ago, when yeast geneticists found genes that control the process, no one could do more than look through a microscope and describe how cells eat themselves. In the first recognizable step of the process, a small, curved, double-membraned structure appears around the parts of the cell that are on the menu. That little bit of membrane grows to encase whatever the cell plans to swallow. “Imagine a teacup expanding and growing and eventually becoming a football” (a soccer ball for Americans), says Sharon Tooze, a cell biologist at Cancer Research UK’s London Research Institute.

That soccer ball structure is the Pac-Man, known technically as an autophagosome. It fuses with another intracellular structure called a lysosome, basically a big bag of enzymes that break down proteins and other molecules into their basic building blocks, much the way stomach acid digests food. The building blocks can then be recycled to build more proteins, membranes or other things the cell needs.