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Mild-mannered metabolic helper rushes to fight invading viruses, researchers report
Date:5/7/2010

c.

When they are not fighting invading microbes, peroxisomes are busy mopping up the potentially damaging free radical byproducts produced by their larger distant cousins, mitochondria, the power plants of the cell. In other house-keeping duties, peroxisomes also make and attach the lipids that grease the cellular machinery so proteins can slide into or through membranes. Both organelles grow, multiply, and shrink in response to metabolic demands.

Peroxisomes acquire their virus-fighting power from a cloak of mitochondrial antiviral signaling protein, or MAVS. Five years ago, MAVS proteins were discovered on mitochondria, a surprising location for which they were named, and shown to be vital to the immune system's ability to fight infections.

MAVS proteins are found in all cells in the body, Kagan said, but until now they were only known to be draped around mitochondria. The latest study started as a search for MAVS on peroxisomes, an idea born from recent reports of other proteins shared by peroxisomes and mitochondria. On a graduate studies sabbatical from Vienna, first author Evelyn Dixit stained cells for MAVS and found the proteins on peroxisomes.

Next, she observed, the same MAVS proteins activated different antiviral immune responses, depending upon the organelle they adorned. "The difference was that the antiviral response was quicker and transient when it originated from peroxisomes compared to mitochondria," Dixit said.

In another difference, the peroxisomal MAVS turned on a subset of antiviral genes without a secreting interferon. By contrast, mitochondrial MAVS triggers interferon production and release, which alerts both the cell and its neighbors to mount a larger immune response.

"Seeing interferon-stimulated genes but no interferon was at first quite aggravating," Dixit said. "We thought we did something wrong. Then we had to turn our thinking around 180 degrees and accept that it was not a mista
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Contact: Bess Andrews
elizabeth.andrews@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

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