A team of Yale researchers has shown that bodies use mitochondria — cell structures typically associated with energy production — to incite immune responses.

The research comes from a team dedicated to the study of mitochondria and is the latest in an expanding body of evidence showing mitochondria do much more than manufacture energy. Working with mice, the team showed inconsequential damage to mitochondria could trigger an antiviral immune response, suggesting that the body may use mitochondria to detect viral infection.

“When the mitochondria DNA is depleted, the host cells respond by inducing genes that are normally induced by type I interferons [genes that are activated only in the presence of specific stimuli],” said Akiko Iwasaki, co-author of the paper and professor of immunobiology at the Yale School of Medicine. “This result was highly unexpected.”

The team modified the expression of the mice’s genes, so the function of certain proteins used in maintaining mitochondrial DNA (mtDNA) — DNA inherited from one’s mother that resides only in mitochondria — was inhibited. They found that the presence of damaged mtDNA in the cytoplasm, the jelly filling of the cell, primed a cell’s immune responses.

The team confirmed that finding when they infected the mice with the herpes simplex virus 1 and vesicular stomatitis virus — a virus that is particularly damaging to mitochondria — and observed the same response.

The research comes as part of a larger effort by the Shadel Lab, directed by Yale professor of pathology and genetics Gerald Shadel, to identify how mitochondria play a role in signaling processes within a cell. The findings were somewhat serendipitous, as the researchers were not expecting the immune response they observed, said Philip West, a postdoctoral researcher in pathology at the Yale School of Medicine.

The researchers began by applying an mtDNA-stressing treatment to the mice, and then identified all of the genes that were being abnormally expressed. They found that most of them were antiviral interferon stimulated genes, but that a similar class of inflammatory genes which code for an immune response was not triggered. West speculated that this phenomenon was caused by the fact that interferon genes are easier to trigger.

This research holds promise for understanding autoimmune disease and lupus, said Shadel, who was also the senior author of the paper. Future research may look into the connection between stressed mtDNA, particularly mtDNA in the cytoplasm of the cell, and lupus.

As for the immediate future, West said he would like to look into the mechanism by which mtDNA is released into the cytoplasm of the cell.

“The genes that came up were broadly antiviral,” he said. “How is mitochondrial DNA stressed and released into the cytoplasm?” is the next question they will tackle, he said.

The paper was published in the journal Nature on Feb. 2.