Researchers catch the molecule triggering inflammation in autoimmune diseases

Summary:  In a medical first, a research team discovered a ‘Great Escape’ made by a rogue molecule thought to be the crucial trigger of inflammation in autoimmune diseases like arthritis. [This article first appeared on LongevityFacts. Author: Brady Hartman. ]

Scientists discovered the exact moment when inflammation-provoking DNA escapes out of the mitochondria during cell death.

The study was published on Feb 26, 2018, in the journal Science by researchers from Monash University in Australia in an international collaboration with the Walter and Eliza Hall Institute and the Howard Hughes Medical Institute.

The research team was headed up by Professor Benjamin Kile with Monash University’s Biomedicine Discovery Institute (BDI), who remarked that

“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. “

Mitochondrial DNA (green) Escaping Mitochondria (red) During Cell Death. Video courtesy of Monash Univ.

Monash research scientist Dr. Kate McArthur was a member of the team who used a revolutionary new microscope to capture the mitochondrion expelling its DNA. Dr. McArthur recalls the moment when she witnessed the event for the first time, saying

“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 I had carefully repeated the experiment many times that I began to realise what we had found,”

Advancements in microscopy techniques are enabling scientists to uncover more of the cell’s hidden secrets. Recently, another group of researchers used a novel microscopy technique to observe fat cells – previously thought to be immobile – moving for the first time and playing a significant role in healing wounds in fruit flies.

Mitochondrial DNA and Inflammation

Mitochondria are the tiny powerhouses of our cells and generate the energy that keeps us alive. However, when they are damaged, they can trigger our immune system with potentially devastating effects. Each cell can contain anywhere from hundreds to thousands of mitochondria, residing in the fluid inside the cell. Mitochondria convert food into an energy-rich molecule called adenosine triphosphate (ATP).

Most people don’t realize that we have two sets of DNA in our bodies, the DNA inside our chromosomes, and the DNA inside our mitochondria that descended from bacteria over a billion years ago.

Because the DNA inside our mitochondria is similar to bacterial DNA, the immune system treats mitochondrial DNA like an invading pathogen. Researchers have long suspected that escaping mitochondrial DNA contributes to autoimmune diseases such as lupus. However, up until the discovery by Monash University, researchers could not explain how it escapes from the mitochondria.

Cells commit suicide all the time as a regular part of the body’s balancing act to eliminate damaged cells.  During this programmed cell death, a process known as apoptosis, a dying cell triggers the release of two proteins called BAK and BAX.  The debris left over by this process can then can contribute to chronic inflammation.

Professor Kile relates the significance of the discovery, saying

“What we witnessed – in real time – was these professional killer proteins opening up huge ‘macropores’ in the outer membrane of the mitochondria, leading the inner contents to herniate out, bringing the mtDNA with it.” adding “BAK and BAX deliver the ‘kill shot’ designed to permanently disable the cell. But in doing that, mtDNA is lost from the mitochondria. In essence, this is collateral damage, which, if it isn’t controlled properly, triggers the immune system to drive pathological inflammation.”

Mighty Mitochondria

The tiny organelle once played a starring role in the mitochondrial theory of aging due to the copious amounts of free radicals they produce. In the last decade, scientists have gained a tremendous amount of new knowledge about mitochondrial DNA and the role of mitochondria in cancer and various human conditions, including Alzheimer’s disease, and dementia. Moreover, researchers suspect that mutations in mitochondrial DNA also play a role in diseases.

The Monash University findings add weight to the notion that mitochondria, either dead or alive, play an essential role in human health.

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References

Cover Photo:  Getty Images.

“DNA gets away: scientists catch the rogue molecule that can trigger autoimmunity.” Monash University. 26 Feb 2018. Link to press release on Scimex.

Kate McArthur et al. “BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science. Vol. 359, Issue 6378, eaao6047. 23 Feb 2018. Link to article in Science.

Disclaimer

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Tags: Cell death, Mitochondrial DNA