January 8, 2003

Food for Thought: Cells Dine on Their Own Brains to Stay Fit and Trim

Eating your own brain may not sound like a sensible approach to prolonging your life, but researchers at the University of Rochester have discovered that some single-celled organisms essentially do just that to keep themselves healthy. The findings are published in this month's issue of Molecular Biology of the Cell.

David Goldfarb, professor of biology at the University of Rochester, studied the yeast Saccharomyces cerevisiae and found that contrary to what biologists have believed, the cell would "eat" its own nucleus to rid itself of aged or damaged sections. Though it's long been known that cells frequently break down and recycle various cell parts in a process called autophagy (after the Greek for "self-eating"), biologists thought that eating the nucleus was strictly off-limits. The nucleus, after all, is sort of the control center of the cell, and where the cell stores its most precious possessions such as its DNA. Eating it would be a bit like lunching on your own brain.

Goldfarb, however, found that the yeast can eat its nucleus by taking it apart piece by piece, removing non-essential bits and leaving behind the essential components such as the chromosomes.

"In human society, the business of collecting and recycling garbage isn't a very glamorous enterprise, but in the less prestige-oriented world of cells, it's invaluable," says Goldfarb. "We now know just how critical this process is, since a unique and elegant autophagic mechanism evolved to allow the piecemeal degradation of an otherwise essential organelle."

Autophagy is really a family of related processes that identify and deliver useful organic molecules, called macromolecules, to the cell's lysozymes or vacuoles. Lysozymes and vacuoles are much like our own stomachs, filled with acid and hydrolytic enzymes capable of reducing macromolecules to their minimal parts. These parts are then shuttled where they are used either to stoke the metabolic fires or as building materials for new macromolecules. The only part of the cell thought to escape this fate is the nucleus, which is as essential to a cell as our brains are to us. Biologists had always thought that taking a bite out of the nucleus would effectively end a cell's life.

Goldfarb found that when the yeast cell wants to recycle some of the macromolecules from its nucleus, it sends a vacuole to pinch off a teardrop-shaped portion of the nucleus and "digest" it. This unique process, called piecemeal microautophagy of the nucleus (PMN), occurs at Velcro-like junctions between the vacuole and the nuclear membranes. Nucleus-vacuole junctions were first described in 2000 by the Rochester group and remain the best-understood, inter-organellar junction apparatus in nature.

"It's possible that PMN may not only recycle damaged or useless portions of the nucleus," says Goldfarb. "It's possible that PMN increases the life span of yeast cells which, like humans, age and die."

Although it's unknown if PMN is at work in human cells, there are a number of cases such as Bloom's disease where pieces of human nuclei are pinched off into the cytoplasm. Scientists have no idea how or why this happens, but the new findings could provide an important foundation on which to build an understanding.

This research was funded by the National Science Foundation and the National Institutes of Health.