A report on the work, done with mouse cells genetically altered to lack the HIF-1 gene, appears in the March 8 issue of Cell Metabolism.
A cell's energy demands are met by two major types of sugar ( glucose) using machines similar to the two types of engines in a hybrid car. One machine, the mitochondrion, is an organelle that breaks down the glucose-using oxygen and produces ATP. The other does the same thing - albeit less efficiently - without using oxygen in a process called glycolysis.
Like the hybrid car, cells use oxygen and the internal combustion engine at higher speeds and rely on an electric engine without need for oxygen consumption at lower speeds. Cells consume glucose through its main energy-producing machine, the mitochondrion, when oxygen is ample. But like the internal combustion engine, this process generates pollutants or toxic oxygen molecules.
At lower oxygen levels, when cells are starved for oxygen - as during exertion or trauma -- the genetic switch that the Hopkins researchers found deliberately shuts off the cell's mitochondrial combustion engine, which scientists had long - and erroneously -- believed ran down on its own due to lack of oxygen.
"The unexpected discovery is that this genetic switch actively shuts off the mitochondrion under low oxygen conditions, apparently to protect cells from mitochondrial toxic oxygen pollutants," said Chi Van Dang, M.D., Ph.D., professor of medicine, cell biology, oncology and pathology, and vice dean for research at the Johns Hopkins Universi
Contact: Eric Vohr
Johns Hopkins Medical Institutions