In experiments with yeast known as S. pombe, the researchers discovered that a gene that helps the organism make cholesterol also helps it survive when oxygen is scarce. The finding, described in the March 25 issue of Cell, offers a new strategy for killing infectious yeast, but it also suggests that cells' efforts to make cholesterol and detect oxygen levels might be connected in people, too.

"We were simply trying to establish that this yeast could be a model for studying cholesterol-related activities in human cells," says the study's leader, Peter Espenshade, Ph.D., assistant professor of cell biology in Johns Hopkins' Institute for Basic Biomedical Sciences. "We certainly didn't expect to find a completely new role for this gene."

It's already well established that human cells can both make cholesterol and sense oxygen. In people, high levels of cholesterol in the blood are a major risk factor for heart disease, and many human cancer cells are able to survive despite being in tumors' oxygen-starved centers.

"We don't know yet whether cholesterol production and oxygen sensing are connected in human cells, but now we're trying to find out," says Espenshade.

In people, the gene in question, known as SREBP, controls other genes whose products help make or import cholesterol. Cholesterol-lowering drugs called statins mimic this gene's natural role by triggering cells to import more cholesterol, clearing the artery-clogging stuff from the blood.

Despite the obvious medical relevance of SREBP, no one had ever looked at the equivalent system -- or even determined whether there was one -- in yeast, the simple, single-celled relatives with which we share many genes. Because yeast can be easily manipulated and studied, Espenshade figure
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
24-Mar-2005