Newly made mitochondrial DNA drives inflammation

[Gondwanaland]

https://www.nature.com/articles/d41586-018-05764-z

Activation of the inflammasome protein complex in immune cells is a key step that triggers an innate immune response. It emerges that the synthesis and oxidation of mitochondrial DNA drives this activation step.

 

[ljimbo423]

This is a very informative article and I think it ties into the biochemical processes of ME/CFS very well. Thank you for posting it.

I have been reading about how mitochondria can cause inflammation for a few months now. My feeling is the inflammation from the dysfunctional mitochondria is playing a big part in ME/CFS symptoms.

Here are a couple more quotes from the paper that jumped out at me-

I think this first quote is referring to why oxidized mitochondrial DNA triggers the cytokine IL-1B and inflammation.

This finding of yet another fascinating link between mitochondria and inflammatory signalling in the innate immune system might reflect the organelle’s early evolutionary origins as a bacterial cell. This inherent otherness could give mitochondria a head start in being recognized as foreign by the innate immune system.

Mitochondria can regulate how immune cells respond to infection and tissue damage.

For example, these organelles can produce pro- or anti-inflammatory signals by altering the levels of metabolites produced in the Krebs cycle2,3, or by changing the level of production of reactive oxygen species (ROS)4,5.

More and more examples are being found of mitochondrial functions being repurposed in unexpected ways to contribute to inflammatory signalling2–5.

This image, as I understand it, shows Reactive oxygen species (ROS) oxidizing mitochondrial DNA and the oxidized mitochondrial DNA triggers inflammasome activation, which causes an increase in Interleukin 1B (IL-1B). Which is a strong innate immune system cytokine.

Something else I find really interesting in the article is that they use lipopolysacchrides (LPS) to cause the ROS and trigger the inflammasome and IL-1B.

 

[Gondwanaland]

This is a very informative article and I think it ties into the biochemical processes of ME/CFS very well. Thank you for posting it.

Thank you for extracting the essentials from it, which I do not have the energy to do.

 

[Gemini]

I think this first quote is referring to why oxidized mitochondrial DNA triggers the cytokine IL-1B and inflammation....Something else I find really interesting in the article is that they use lipopolysacchrides (LPS) to cause the ROS and trigger the inflammasome and IL-1B.

Thanks for pointing out the IL-1B trigger @ljimbo423. Very interesting!

Montoya's recent paper profiling cytokines 18 hours post exercise cites IL-1B:

The most discriminatory cytokines post exercise were CD40L, platelet activator inhibitor, interleukin 1-β, interferon-α and CXCL1.

In conclusion, cytokine profiling following exercise may help differentiate patients with ME/CFS from sedentary controls.

https://www.ncbi.nlm.nih.gov/pubmed/29426834

 

[ljimbo423]

The most discriminatory cytokines post exercise were CD40L, platelet activator inhibitor, interleukin 1-β, interferon-α and CXCL1.

In conclusion, cytokine profiling following exercise may help differentiate patients with ME/CFS from sedentary controls.

Nice find! I think exercise in ongoing research will reveal a lot.

 

[Wishful]

It certainly helps show how complex the whole immune system is. I was convinced that my disorder involved mitochondria and the immune system long before I realized I had ME, so this new finding fits that nicely. This should give the researchers another perspective on ME.

 

[Gemini]

I think exercise in ongoing research will reveal a lot.

Agree @ljimbo423 glad you mentioned exercise, prompted me to take another look at Maureen Hanson's recent Iime Conference talk covering her research and "microvesicule" project. This article mentions them:

"Mitochondria can release microvesicles containing oxidized DNA and protein...the release of mitochondrial nucleic acids to the cytoplasm can act as a signal that triggers a defense response..."

Thanks for posting this @Gondwanaland! Fascinating link between mitochondrial and inflammatory signaling! In a top scientific journal! Stanford co-authors on the underlying Nature paper, too.

Summary transcript of Hanson's talk here:
www.investinme.eu/Iimec13.shtml#report

Hanson's entire talk is available on DVD that can be ordered:
www.investinme.eu/Iimec13.shtml#dvd