Investigating the ‘faulty batteries’ inside cells

What is this research looking at?

Mitochondria are the ‘batteries’ inside living cells which help maintain their health and function. However, the mitochondria inside the cells lining the large bowel are exposed to many things which may damage them. In healthy people, these damaged ‘faulty batteries’ are recycled or packaged away so they can be safely disposed. Research has already shown that in people with Inflammatory Bowel Disease (IBD) these processes do not work properly and the unhealthy colon leaks the damaged mitochondria into the internal environment of the cell and into the blood stream. Mitochondria have many similar properties with bacteria and as such the immune system can get confused by their unexpected presence in the blood and perhaps induce an immune response. When the damaged mitochondria escape from the colons of people with IBD they seems to act as a ‘danger signal’, triggering inflammation, and leading to an influx of inflammatory cells to the site where the damaged mitochondria have leaked from. Previous research on blood samples from unwell individuals in intensive care has shown increased levels of DNA from damaged mitochondria, and they may directly contribute to causing inflammation.    

The researchers want to use this information to investigate the importance of the damaged mitochondria in driving inflammation in people with IBD. They already have data showing high levels of mitochondrial DNA when people have active IBD. They will use a large number of samples from patients with IBD to establish the relationship, and then try and characterise the pattern of mitochondria damage associated molecular patterns which trigger the immune system. It may be possible to block the inflammatory signal caused by the damaged mitochondria in some patients, and the aim of the study is to find which patients this would work best in, which may eventually lead to a larger study looking at whether blocking the gut mitochondria signalling may be used as a new IBD therapy. 

Conclusions:
The researchers were able to confirm their previous finding that people with IBD have high levels of mitochondrial DNA – but this time they were able to look in a much larger number of people. They also found that mitochondrial DNA levels are particularly high in people with more severe forms of IBD. They will now investigate if mitochondrial DNA can be used as a biomarker (a measurable biological signal or flag). Furthermore, future research will determine whether the mitochondrial DNA activates the immune system through a particular receptor (a special structure found on the surface of cells) called toll-like 9 receptor. Triggering the immune system through this particular receptor is thought make Ulcerative Colitis more severe – so a treatment that blocks it could provide a novel treatment option for patients. 

What do researchers think this could mean for people with IBD? 

The researchers hope that investigating damaged mitochondria pathways may lead to exciting new IBD therapies. Clinical trials based on blocking the pathway of damaged mitochondria may take place within the next five to ten years. 

Who is leading this research: Dr Gwo-Tzer Ho, University of Edinburgh
Our Funding: £8000
Duration: 12 months
Official title of application: Investigating the role of mitochondrial damage associated molecular patterns (mDAMPs) in the pathogenesis of IBD
Tags: Cause of IBD