While studying how a cell keeps its genetic material intact, scientists at Johns Hopkins got busy alternately knocking out two catalysts vital to managing a yeast cell's energy. They discovered to their complete surprise that the removal of one of them led the cell to turn off 70 percent of its 5,000 genes and die.
"We were completely unprepared for such a dramatic event," says Jef Boeke, Ph.D., Sc.D., a professor of molecular biology and genetics at Hopkins and author of the study. "We've never seen anything that can turn off that many genes in a cell at once."
The unexpected finding linking both gene usage and energy management machinery is "like finding out that an enzyme that breaks down food in the stomach also helps you remember telephone numbers or that preventing such digestion makes you forget them," Boeke added.
The research, to be published in the July 21 issue of Molecular Cell, could lead to new strategies one day to slow aging and treat cancer, events closely linked to changes in gene control and energy metabolism.
Working at the High Throughput Biology Center of the Institute for Basic Biomedical Sciences at Hopkins, Boeke's team uses yeast almost exclusively for such studies because even though they are single-celled organisms, they grow quickly, are easy to analyze in the lab, and contain many genes and biological processes present in other animals, including humans.
For example, like all animal cells, yeast use sugar as an energy source. To harvest the energy contained in sugar, the yeast must convert the sugar into other molecules in a series of biochemical steps helped along the way by enzymes that make each step happen faster.
Focusing on two of these enzymes, closely related to each other, the research team separately removed each from the yeast cells to see if either or both were essential to the cell's survival.
The researchers found that one of these enzymes - called Acs1p - which is generally inactive had little apparent impact when they removed it. "The yeast seemed relatively unscathed," said Boeke.
But when they knocked out the other one - called Asc2p - the yeast cells died. That made it clear that this enzyme is critical for survival.
Further analysis with high-power microscopes revealed that this second enzyme, Asc2p, was residing - unexpectedly -- in the part of the cell housing its genetic material - its chromosomes - rather than in the part of the cell - the mitochondria -- that harvests energy from sugar.
But why would an enzyme involved in generating energy live in the "wrong" part of the cell? A closer look at the chromosomal and non-chromosomal parts of the cell showed that although the enzyme itself is found only in the former, the chemical made by it is found in both places.