According to the researchers, the new role makes perfect biological and evolutionary sense because it fits well with another function of mitochondria as executioners of a biochemical cascade that causes programmed cell death, or apoptosis.

"This is the first protein known to be involved in the immune response that is found in mitochondria," said Zhijian 'James' Chen, a Howard Hughes Medical Institute investigator at the University of Texas Southwestern Medical Center. Chen and his colleagues reported the discovery on August 25, 2005, in an immediate early publication of the journal Cell.

In their studies, Chen and his colleagues were seeking a regulatory molecule that would provide a missing link in the activation of two important triggers of the innate immune system -- NF-B and IRF3. Somehow, these molecules are activated in response to a receptor molecule, called RIG-I, which detects viral genetic material. RIG-I binds to the RNA of viruses such as the influenza virus, hepatitis C virus, West Nile virus and SARS virus.

The researchers knew the molecule they were seeking was present in a biochemical pathway somewhere between RIG-I and other "downstream" regulatory molecules. They initiated a search for this missing molecule by searching for proteins in the cell that contain a characteristic molecular domain, called a CARD domain, which mediates interactions between different regulatory proteins. Their search yielded a protein, which they called MAVS for mitochondrial antiviral signaling.

Their experiments revealed that MAVS activated NF-B and IRF3 in cell cultures. They also found that in order for MAVS to function, it requires both the CARD domain and another doma
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
25-Aug-2005