Article: DNA gets away: Scientists catch the rogue molecule that can trigger autoimmunity

Indigophoton

Indigophoton

Senior Member (Voting Rights)
I thought this was interesting, the significant discovery of how mitochondrial DNA ends up outside the mitochondria, where it can potentially trigger autoimmune conditions.

A research team has discovered the process - and filmed the actual moment - that can change the body's response to a dying cell. Importantly, what they call the 'Great Escape' moment may one day prove to be the crucial trigger for autoimmune diseases like arthritis.

The research team, led by Professor Benjamin Kile from Monash University's Biomedicine Discovery Institute (BDI), has discovered - and filmed - the exact moment when DNA escapes out of the mitochondria (the organelles inside cells that produce energy) during cell death. The study, published today in the journal Science, involved major collaborators from the Walter and Eliza Hall Institute and the Howard Hughes Medical Institute's Janelia Research Campus in the US.

Mitochondria are the ultimate double agent; they are essential to keep cells alive, but when damaged, they can trigger the body's own immune system with potentially devastating consequences.
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The live-cell lattice light-sheet microscopy (LLSM) system developed by Nobel Prize winner Eric Betzig is a new technique that allows scientists to observe living cells at groundbreaking resolution. Dr McArthur travelled to the Janelia Research Campus in Virginia multiple times between 2015-2017, and remembers the moment when she witnessed, for the first time, the mitochondria actively expelling its DNA.

"As scientists, we are taught to be quite sceptical when we see something unexpected, so I think my initial reaction was 'no way. It was only after we had repeated the experiment many times that I began to realise what we had found," Dr McArthur said.
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Professor Kile stressed that, in research, "fundamental discoveries such as this are rare, and this one has profound implications for the understanding of a wide range of autoimmune diseases and infections.
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https://medicalxpress.com/news/2018-02-dna-scientists-rogue-molecule-trigger.amp?

There is a video clip showing the process in action at the link.
 
Blobs vomiting... Does seeing this happen make any difference to anything at all when it was already known to happen or is this just interesting trivia?
 
Skycloud said:
Blobs vomiting... Does seeing this happen make any difference to anything at all when it was already known to happen or is this just interesting trivia?
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It is always good to see how things actually work in detail but I cannot see how it adds to our understanding of immune processes particularly. What is sometimes important is to understand the way events occur in microcompartments. This may clarify that.
 
Alvin said:
I just read what was posted above but if this is such an easy thing to happen would it not be common and discovered long before now?
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I think it's a potential piece of the puzzle which has been presumed to happen before in one theory of autoimmunity, but not actually observed as it happens. This is what Wikipedia says about the method used to detect the escaping DNA:
Lattice light-sheet microscopy is a modified version of light sheet fluorescence microscopy that increases image acquisition speed while decreasing damage to cells caused by phototoxicity. This is achieved by using a structured light sheet to excite fluorescence in successive planes of a specimen, generating a time series of 3D images which can provide information about dynamic biological processes.

It was developed in the early 2010s by Eric Betzig. According to the Washington Post, Eric Betzig believes that this development will have a greater impact than the work that earned him the 2014 Nobel Prize in Chemistry for "the development of super-resolved fluorescence microscopy".
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Mitochondrial DNA is of particular interest in regard to immune reactions because it's derived from bacterial DNA. Segments of it escaping from cells may look like a foreign invader to parts of our immune systems.
 
Skycloud said:
I do find it interesting that things like this can be seen, but didn't see why it might be a good thing beyond 'oh wow look at that'
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It means going beyond "maybe this could happen" to confirming that it does happen or alternatively disproving that it could be what's happening. What happens inside living cells is extremely important, but it can be very hard to study.
 
I thought it was interesting , although I don't think it proves the link with autoimmunity theory though. We have had mitochondria in our cells for a very long long time. Just observing it happen doesn't explain what the significance is?

The evolutionary theory of mitochondria and chloroplasts also has some fairly loose, yet to be proven assumptions in it and we haven't really got an answer for how this happened; rather that it was a long time ago in the case of mitochondria (although I personally think its plausible). Creating hypothesis this far back in evolutionary history tends to bE problematic since its best guess. I thought that mitochondrial sequencing work never revealed any genetic heritage or links with modern day bacteria, so that seems to suggest the theory is based on a high degree of speculation.
 
Valentijn said:
I think it's a potential piece of the puzzle which has been presumed to happen before in one theory of autoimmunity, but not actually observed as it happens. This is what Wikipedia says about the method used to detect the escaping DNA:
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Fair enough
Mitochondrial DNA is of particular interest in regard to immune reactions because it's derived from bacterial DNA. Segments of it escaping from cells may look like a foreign invader to parts of our immune systems.
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I would hope our bodies are attuned to having mitochondria by now but who knows this may turn out to be a big piece of a puzzle.
 
https://www.theage.com.au/national/...tage-inside-a-human-cell-20180222-p4z1bg.html. A similar article but, as a non-scientist, I found it more coherent. Professor Kile describes how this discovery could possibly lead to treatments.

"It is thought some of this ejected DNA makes its way outside the cell and into the blood.

This might explain why the immune system in some people seems to go haywire, causing illnesses like rheumatoid arthritis and diabetes. Possibly, Professor Kile suggests, the immune system is reacting to the presence of the foreign mitochondrial DNA.

The find, a “fundamental discovery”, will be used by researchers studying the cause of – and treatments for – autoimmune diseases, says Professor Kile.

But Professor Kile has a more radical idea: tuning the system to fight cancer.

If you could get somehow get cancerous cells to release their mitochondrial DNA, you could provoke an enormous immune response against the cells in the tumour.

“This horrible autoimmune response we want to prevent in healthy people, that could be triggered to fight cancer,” he says."
 
oldtimer said:
The find, a “fundamental discovery”, will be used by researchers studying the cause of – and treatments for – autoimmune diseases, says Professor Kile.
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Sorry, but I think this is just naive hype. The autoimmune bit is based on very old tired trite ideas about how autoimmunity comes about that have proved to have no basis.There is also a confusion here between the innate immune response - to bacterial DNA sequences such as CPG - and the adaptive immune responses of autoimmunity. I was surrounded by simplistic ideas like this throughout my career and fortunately managed to ignore them and work out some real mechanisms.
 
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