Johns Hopkins researchers find link between cell's energy use and genome health

Another possible link between diet and aging

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."

[...]

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

[...]

When the research team removed the enzyme Asc2p that makes acetyl-CoA from yeast cells, they predicted, if they were right about why the enzyme and its chemical product are found near chromosomes, that the chromosomes would have less acetyl-CoA. Less acetyl-CoA, they reasoned, could cause DNA to be more tightly wrapped in chromosomes, and this might lead to genes being turned off. That is exactly what they found when they looked at the more than 5,000 genes in the yeast cells lacking this enzyme. More than 70 percent of them were indeed turned off.

According to Boeke, other studies have shown that reducing the number of calories a yeast cell "eats" not only can affect chromosomes, but also increase lifespan, allowing the yeast to live longer, an observation that fits their findings. .