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)
How the right
nibble away at themselves via Pac-Man–
like structures (green and yellow). DININGIN
amount of cellular
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
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
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.
Since biologists working with yeast
discovered the first genes involved in
Andrey Tsve Tkov, s Teven Finkbeiner, UCsF