Researchers at Johns Hopkins have discovered how cells fine-tune their oxygen use to make do with whatever amount is available at the moment.
Too little oxygen threatens life by compromising mitochondria that power it, so when oxygen is scarce, cells appear to adjust by replacing one protein with an energy-efficient substitute that "is specialized to keep the motor running smoothly even as it begins to run out of gas," says Gregg Semenza, M.D., Ph.D., a professor of pediatrics and director of the vascular biology program in the Institute for Cell Engineering at Hopkins. "This is one way that cells maintain energy production under less than ideal conditions." A report on the work is in the April 6 issue of Cell.
"Cells require a constant supply of oxygen," Semenza says, "so it's vital for them to quickly react to slight changes in oxygen levels." The protein-swap is how they do it.
In the mitochondria, the tiny powerhouses found in every cell, energy is produced by passing electrons through a series of relay stations called cytochromes until they eventually join with oxygen to form water. This final step is directed by the protein cytochrome coxidase, or COX for short. If electrons react with oxygen before reaching COX, they generate "free radicals" that can damage or destroy cells. The mitochondria are designed to produce energy without excess free radical production at normal oxygen levels.
Semenza's team noticed that one particular component of the COX protein complex, COX4, comes in two different forms, COX4-1 and COX4-2. Under normal oxygen conditions, the cells' mitochondria contain mostly COX4-1. The researchers suspected that COX 4-2 might be the active protein under stressful, low-oxygen conditions, which the researchers refer to as hypoxia.
To test the idea, the team compared the growth of human cells in normal oxygen conditions (what's generally present in normal room air) compared to cells grown
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Contact: Audrey Huang
audrey@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
5-Apr-2007