Back Understanding Autoimmune Disease
Understanding Autoimmune Disease
Back Resources for Hope & Health
Resources for Hope & Health
Back Autoimmune Research & News
Autoimmune Research & News
Back Who We Are & How We Help
Who We Are & How We Help
an icon of a microscope, indicating research and science
Research Grants
& Projects

Decoding Inflammation: Mitochondrial Triggers in Autoimmunity

August 9, 2022

Inflammation is a normal part of an immune response that helps fight infections and subsides once an infection has been eliminated. However, in individuals with autoimmunity, inflammation becomes chronic and contributes to symptoms and damage. Research has been focused on understanding the triggers of inflammation in autoimmune disease patients. One such trigger has been identified as mitochondrial DNA (mtDNA).

Mitochondria are the part of the cell that generates the energy needed to fuel body processes. It contains its own unique DNA (mtDNA). The mtDNA usually stays inside the mitochondria. Prior work has shown that mtDNA can trigger inflammation when it escapes. This work has also shown that there are elevated levels of mtDNA in the cells and blood of patients with certain autoimmune diseases. However, how the mtDNA exits is still unclear.

A study titled Oxidized DNA fragments exit mitochondria via mPTP- and VDAC-dependent channels to activate NLRP3 inflammasome and interferon signaling published in Immunity, has helped answer this question. In this study, researchers used mice and cell culture to investigate how mtDNA escapes the mitochondria and triggers inflammation. They found that when mitochondria are stressed, some of the mtDNA becomes damaged and is subsequently cut by an enzyme named FEN1. Then, channels open in the mitochondria that allow it to exit. Once mtDNA is in the cytoplasm, it triggers NLRP3 inflammasome activation, cGAS-STING activation, and interferon signaling which generates inflammation. 

These are valuable findings, as they help us understand how mtDNA escapes and triggers inflammation. Now that these processes are known, further studies may lead to therapeutics that reduce inflammation in patients by targeting these processes.

Citation for report:

Xian, H., Watari, K., Sanchez-Lopez, E., Offenberger, J., Onyuru, J., Sampath, H., Ying, W., Hoffman, H. M., Shadel, G. S., & Karin, M. (2022). Oxidized DNA fragments exit mitochondria via mPTP- and VDAC-dependent channels to activate NLRP3 inflammasome and interferon signaling. Immunity, 55(8), 1370–1385.e8. https://doi.org/10.1016/j.immuni.2022.06.007.