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 discovered – and filmed – the exact moment when DNA escapes out of the mitochondria during cell death.
The study, published in Science, was led by Professor Benjamin Kile from Monash University’s Biomedicine Discovery Institute (BDI) and was a collaboration between the Walter and Eliza Hall Institute and Monash BDI, with the Howard Hughes Medical Institute (HHMI) Janelia Research Campus, US.
Mitochondria – the cell machinery that produce energy – 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. The DNA inside mitochondria (mtDNA) has many similarities with bacterial DNA, and the body reacts to its presence outside the mitochondria, or indeed outside the cell, as if under attack from invading pathogens. A similar failure to distinguish ‘self’ from ‘non-self’ underlies inflammatory and autoimmune diseases.
New technology captures Great Escape
While the release of mtDNA is thought to contribute to autoimmune diseases such as lupus, how it escapes from the mitochondria has never been explained. Monash BDI researcher Dr Kate McArthur, while completing her PhD at the Walter and Eliza Hall Institute, and Institute co-author Dr Lachlan Whitehead used a revolutionary new microscope to capture the moment when mitochondria form a ‘hernia’ that balloons out of the mitochondria, expelling the DNA into the rest of the cell.
The live-cell lattice light-sheet microscope – developed by Nobel Prize winner Eric Betzig – is a new technique that allows scientists to observe living cells at groundbreaking resolution.
Dr McArthur, who traveled to the HHMI Janelia Research Campus multiple times between 2015 and 2017, remembers the moment when she witnessed, for the first time, the mitochondria actively expelling its DNA.
“As scientists, we are taught to be quite skeptical 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,” she said.
A revolution in microscopy
With the lattice light-sheet microscope researchers can watch the inner workings of living cells with unprecedented detail and in ‘real time’; a groundbreaking achievement that has enabled research that – until now – was simply not possible.
Institute researchers Dr Lachlan Whitehead, Dr Niall Geoghegan and Dr Kelly Rogers, who were co-authors on the paper, spent seven months building the Institute’s lattice light-sheet microscope. It is the only custom-built microscope of its kind in Australia and was used in the final stages of the project.
Without the lattice light-sheet microscope technology, this research would not have been possible, Dr Rogers said.
“Imagine looking at a picture from the AFL Grand Final and trying to understand what happened from that one picture that captures one second of the game. It isn’t possible.
“With the lattice light-sheet, we can watch the whole match in real time and in high definition. It is a game changer,” Dr Rogers said.
Professor Kile said when a cell committed suicide – a normal part of the human body’s balancing act to control blood cell numbers – two proteins called BAK and BAX were triggered.
“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, and bringing the mtDNA with it,” Professor Kile said.
“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,” he said.
The discovery was cemented by images captured by Monash University’s Titan Krios cryo-electron microscope, currently the most advanced microscope for biological electron microscopy, and the Walter and Eliza Hall Institute’s new, custom-built lattice light-sheet microscope.
The Latest on: Autoimmunity
Controlling B-cell Numbers, Activity Key to Preventing Inflammation in MS, Study Suggests
on November 12, 2018 at 4:30 am
The study, “Myeloid-derived suppressor cells control B cell accumulation in the central nervous system during autoimmunity,” was published in the journal Nature Immunology. Fine-tuned ... […]
Applied DNA Subsidiary LineaRx Provides Cost And Quality Advantages To Technogenetics Diagnostic Solutions
on November 8, 2018 at 10:33 pm
that produces and sells kits to detect autoimmunity and infectious diseases. The purified, PCR-produced DNA is custom-made for Technogenetics and is used to prepare the basic component responsible for ... […]
An IgG1 SNP enhances autoimmunity
on November 8, 2018 at 10:10 pm
One common feature of autoimmune diseases like systemic lupus erythematosus (SLE) is the presence of high titers of self-reactive antibodies. These result in immune complexes, inflammation, and tissue ... […]
Overexpression of the Cytokine BAFF and Autoimmunity Risk
on November 1, 2018 at 3:20 pm
Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and ... […]
Apellis Advances On Autoimmunity
on October 4, 2018 at 7:00 am
Deliberate invention, aimed at starting a biopharma business, can be a valid, creative, and sometimes rewarding enterprise. Many or perhaps most of the companies in this space begin as a scientific co... […]
Community Health Event at Allegheny Health Network’s Autoimmunity Institute to Shine Light on Relapsing Polychondritis
on September 21, 2018 at 6:12 am
Relapsing Polychondritis Awareness and Support Foundation Inc. (RPASF) and Race for RP encourage the community to attend this event at Allegheny Health Network (AHN) in Pittsburgh featuring the nation ... […]
Biochemists described a new mechanism for autoimmunity suppression
on September 10, 2018 at 5:52 am
Plastic plate with medium for cell growth. Credit: Dmitry Zhdanov RUDN biochemists suggested a new mechanism by which the human body prevents the development of autoimmune diseases, allergies and impl... […]
Autoimmunity plays role in development of COPD, study finds
on August 16, 2018 at 11:25 am
Micrograph showing emphysema (left – large empty spaces) and lung tissue with relative preservation of the alveoli (right). Credit: Wikipedia Autoimmunity plays a role in the development of chronic ob... […]
Autoimmunity may lead to skin ailments: Docs
on August 12, 2018 at 1:45 pm
CHANDIGARH: Autoimmune diseases are commonly known to weaken the body’s fighting mechanism and thereby affect the organs. But what is rarely known is that these diseases mostly attack the skin. To spr... […]
via Google News and Bing News